Cell Therapy for Metastatic Melanoma Using CD8 Enriched Tumor Infiltrating Lymphocytes

• ClinicalTrials.gov Identifier: NCT01236573
• Recruitment Status: Terminated
• First Posted: November 7, 2010
• Results First Posted: October 26, 2015
• Last Update Posted: November 26, 2015
• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC)

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Skin Cancer; Metastatic Melanoma
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: IL-12 transduced TIL
• Enrollment: 34

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)	Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)	Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)	Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)	Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)	Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)	Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)	Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)	Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)	Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)	Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Arm/Group Description	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
Period Title: Phase 1-Dose Escalation-Cohorts 1-4
Started	1	1	6	1	0	0	0	0	0	0	0
Completed	1	1	6	1	0	0	0	0	0	0	0
Not Completed	0	0	0	0	0	0	0	0	0	0	0
Period Title: Phase 1-Dose Escalation-Cohorts 5-10
Started	0	0	0	0	1	4	3	3	4	4	0
Completed	0	0	0	0	1	4	2	3	2	3	0
Not Completed	0	0	0	0	0	0	1	0	2	1	0
Reason Not Completed
Death during treatment	0	0	0	0	0	0	1	0	1	1	0
Not treated	0	0	0	0	0	0	0	0	1	0	0
Period Title: Phase 2- MTD/Anti-IL-12 Cells-Cohort 11
Started	0	0	0	0	0	0	0	0	0	0	6
Completed	0	0	0	0	0	0	0	0	0	0	5
Not Completed	0	0	0	0	0	0	0	0	0	0	1
Reason Not Completed
Did not receive cells	0	0	0	0	0	0	0	0	0	0	1

Baseline Characteristics

Arm/Group Title		Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)	Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)	Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)	Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)	Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)	Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)	Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)	Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)	Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)	Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)	Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)	Total
Arm/Group Description		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Total of all reporting groups
Overall Number of Baseline Participants		1	1	6	1	1	4	3	3	4	4	6	34
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	6 participants	1 participants	1 participants	4 participants	3 participants	3 participants	4 participants	4 participants	6 participants	34 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	1 100.0%	1 100.0%	6 100.0%	1 100.0%	1 100.0%	4 100.0%	3 100.0%	3 100.0%	3 75.0%	3 75.0%	5 83.3%	31 91.2%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 25.0%	1 25.0%	1 16.7%	3 8.8%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1 participants	1 participants	6 participants	1 participants	1 participants	4 participants	3 participants	3 participants	4 participants	4 participants	6 participants	34 participants
		56.0 (0)	50.0 (0)	39.0 (11.5)	48.0 (0)	60.0 (0)	57.3 (10.9)	49.0 (14.5)	56.0 (9.6)	53.5 (16.2)	55.8 (12.2)	49.3 (16.5)	50.7 (13.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	6 participants	1 participants	1 participants	4 participants	3 participants	3 participants	4 participants	4 participants	6 participants	34 participants
	Female	1 100.0%	0 0.0%	1 16.7%	0 0.0%	0 0.0%	1 25.0%	2 66.7%	1 33.3%	1 25.0%	2 50.0%	0 0.0%	9 26.5%
	Male	0 0.0%	1 100.0%	5 83.3%	1 100.0%	1 100.0%	3 75.0%	1 33.3%	2 66.7%	3 75.0%	2 50.0%	6 100.0%	25 73.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	6 participants	1 participants	1 participants	4 participants	3 participants	3 participants	4 participants	4 participants	6 participants	34 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	1 25.0%	0 0.0%	2 5.9%
	Not Hispanic or Latino	1 100.0%	1 100.0%	6 100.0%	1 100.0%	1 100.0%	4 100.0%	3 100.0%	2 66.7%	4 100.0%	3 75.0%	6 100.0%	32 94.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	6 participants	1 participants	1 participants	4 participants	3 participants	3 participants	4 participants	4 participants	6 participants	34 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	1 100.0%	1 100.0%	6 100.0%	1 100.0%	1 100.0%	4 100.0%	3 100.0%	3 100.0%	4 100.0%	3 75.0%	6 100.0%	33 97.1%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 25.0%	0 0.0%	1 2.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	1 participants	1 participants	6 participants	1 participants	1 participants	4 participants	3 participants	3 participants	4 participants	4 participants	6 participants	34 participants
		1	1	6	1	1	4	3	3	4	4	6	34

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD)
Description	The MTD was determined by evaluating dose limiting toxicities (DLT) of participants that received increasing doses of intravenous infusion of IL-12 gene transduced tumor infiltrating lymphocytes (TIL) (i.e., 1x10^6, 3x10^6, 3x10^7, 1x10^7, 3x10^7, 1x10^8, 3x10^8, 1x10^9, and 3x10^9) in cohorts 1-10. Maximum tolerated cell dose is the highest dose at which </= 1 of 6 patients experienced a DLT (i.e. grade 2 or greater allergic reaction)).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Phase I Participants
Arm/Group Description:	All phase I participants who received at least one dose intravenously of CD8 + TIL expressing IL-12 in Groups 1-4, and Bulk TIL expressing IL-12 in Groups 5-10 (i.e., CD8 + TIL expressing IL-12 1x10^6, CD8 + TIL expressing IL-12 3x10^6, CD8 + TIL expressing IL-12 3x10^7, CD8 + TIL expressing IL-12 3x10^7, Bulk TIL expressing IL-12 1x10^7, Bulk TIL expressing IL-12 3x10^7, Bulk TIL expressing IL-12 1x10^8, Bulk TIL expressing IL-12 3x10^8, Bulk TIL expressing IL-12 1x10^9, and Bulk TIL expressing IL-12 3x10^9) respectively.
Overall Number of Participants Analyzed	28
Measure Type: Number; Unit of Measure: Cells
	1,000,000,000

2. Primary Outcome

Title	Response (Complete Response (CR) + Partial Response (PR)) to Therapy
Description	Response was determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline um LD. Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)	Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)	Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)	Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)	Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)	Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)	Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)	Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)	Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)	Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)	Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Arm/Group Description:	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
Overall Number of Participants Analyzed	1	1	6	1	1	4	3	3	4	4	6
Measure Type: Number; Unit of Measure: participants
Complete Response (CR)	0	0	0	0	0	0	0	0	0	1	0
Partial Response (PR)	0	0	0	0	0	0	0	0	1	3	1
Progressive Disease (PD)	1	1	6	0	1	4	2	2	2	0	3
Not Assessed (NA)	0	0	0	1	0	0	1	1	1	0	1
Not Evaluable (NE)	0	0	0	0	0	0	0	0	0	0	1

3. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame	49 months and 20 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)	Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)	Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)	Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)	Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)	Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)	Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)	Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)	Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)	Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)	Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Arm/Group Description:	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
Overall Number of Participants Analyzed	1	1	6	1	1	4	3	3	4	4	6
Measure Type: Number; Unit of Measure: participants
	1	1	6	1	1	4	3	3	4	4	6

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)		Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)		Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)		Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)		Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)		Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)		Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)		Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)		Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)		Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)		Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Arm/Group Description	Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.		Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr. IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
All-Cause Mortality
	Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)		Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)		Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)		Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)		Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)		Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)		Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)		Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)		Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)		Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)		Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--		--/--		--/--		--/--		--/--		--/--		--/--		--/--
Serious Adverse Events
	Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)		Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)		Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)		Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)		Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)		Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)		Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)		Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)		Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)		Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)		Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0.00%)		0/1 (0.00%)		2/6 (33.33%)		0/1 (0.00%)		0/1 (0.00%)		0/4 (0.00%)		1/3 (33.33%)		1/3 (33.33%)		1/4 (25.00%)		1/4 (25.00%)		2/6 (33.33%)
Blood and lymphatic system disorders
Platelets † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Hemoglobin † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0x10e9/L) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Metabolism and nutrition disorders
Bilirubin (Hyperbilirubinemia) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Creatinine † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
ALT, SGPT (serum glutamic pyruvic transaminase) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1
AST, SGOT (serum glutamic oxaloacetic transaminase) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	2/6 (33.33%)	2
Respiratory, thoracic and mediastinal disorders
Hypoxia † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Dyspnea (shortness of breath) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Pneumonitis/pulmonary infiltrates † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Vascular disorders
Thrombosis/thrombus/embolism † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Thrombotic microangiopathy † 1 [1]	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE (3.0); [1] (e.g., thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)		Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)		Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)		Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)		Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)		Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)		Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)		Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)		Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)		Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)		Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)		1/1 (100.00%)		6/6 (100.00%)		1/1 (100.00%)		1/1 (100.00%)		4/4 (100.00%)		3/3 (100.00%)		3/3 (100.00%)		4/4 (100.00%)		4/4 (100.00%)		6/6 (100.00%)
Blood and lymphatic system disorders
PTT (Partial Thromboplastin TIme) † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	4/6 (66.67%)	4	1/1 (100.00%)	1	1/1 (100.00%)	1	2/4 (50.00%)	2	2/3 (66.67%)	2	2/3 (66.67%)	2	3/4 (75.00%)	3	1/4 (25.00%)	1	0/6 (0.00%)	0
Hemoglobin † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	6/6 (100.00%)	6	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	2/3 (66.67%)	2	3/3 (100.00%)	3	4/4 (100.00%)	4	4/4 (100.00%)	4	3/6 (50.00%)	3
Leukocytes (total WBC) † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	6/6 (100.00%)	6	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	3/3 (100.00%)	3	3/3 (100.00%)	3	4/4 (100.00%)	4	4/4 (100.00%)	4	6/6 (100.00%)	6
Lymphopenia † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	6/6 (100.00%)	6	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	3/3 (100.00%)	3	3/3 (100.00%)	3	4/4 (100.00%)	4	4/4 (100.00%)	4	6/6 (100.00%)	6
Neutrophils/granulocytes (ANC/AGC) † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	6/6 (100.00%)	6	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	3/3 (100.00%)	3	3/3 (100.00%)	3	4/4 (100.00%)	4	3/4 (75.00%)	3	6/6 (100.00%)	6
Platelets † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	5/6 (83.33%)	5	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	2/3 (66.67%)	2	3/3 (100.00%)	3	4/4 (100.00%)	4	4/4 (100.00%)	4	6/6 (100.00%)	6
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) † 1	1/1 (100.00%)	1	0/1 (0.00%)	0	5/6 (83.33%)	5	1/1 (100.00%)	1	1/1 (100.00%)	1	3/4 (75.00%)	3	1/3 (33.33%)	1	3/3 (100.00%)	3	3/4 (75.00%)	3	4/4 (100.00%)	4	0/6 (0.00%)	0
Coagulation-Other (thrombotic microangiopathy) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Edema:limb † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Cardiac disorders
Supraventricular and nodal arrhythmia † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	2/4 (50.00%)	2	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Pleural effusion (non-malignant) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	1/6 (16.67%)	1
Hypertension † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Hypotension † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	1/4 (25.00%)	1	0/6 (0.00%)	0
Eye disorders
Vision-blurred vision † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Gastrointestinal disorders
Nausea † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	4/6 (66.67%)	4	1/1 (100.00%)	1	1/1 (100.00%)	1	3/4 (75.00%)	3	3/3 (100.00%)	3	3/3 (100.00%)	3	4/4 (100.00%)	4	4/4 (100.00%)	4	3/6 (50.00%)	3
Vomiting † 1	1/1 (100.00%)	1	0/1 (0.00%)	0	4/6 (66.67%)	4	1/1 (100.00%)	1	1/1 (100.00%)	1	3/4 (75.00%)	3	3/3 (100.00%)	3	3/3 (100.00%)	3	3/4 (75.00%)	3	1/4 (25.00%)	1	2/6 (33.33%)	2
Dry mouth/salivary gland (xerostomia) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Hemorrhage, GI † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	2/3 (66.67%)	2	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Gastrointestinal -Other (bloating) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Gastritis (including bile reflux gastritis) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Taste alteration (dysgeusia) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Constipation † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	1/6 (16.67%)	1
Diarrhea † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	2/6 (33.33%)	2	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	2/3 (66.67%)	2	2/3 (66.67%)	2	2/4 (50.00%)	2	3/4 (75.00%)	3	2/6 (33.33%)	2
Mucositis/stomatitis (clinical exam) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	1/6 (16.67%)	1
Anorexia † 1	0/1 (0.00%)	0	1/1 (100.00%)	1	6/6 (100.00%)	6	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	3/3 (100.00%)	3	2/3 (66.67%)	2	2/4 (50.00%)	2	2/4 (50.00%)	2	1/6 (16.67%)	1
General disorders
Pain † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	6/6 (100.00%)	6	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	3/3 (100.00%)	3	3/3 (100.00%)	3	3/4 (75.00%)	3	4/4 (100.00%)	4	3/6 (50.00%)	3
Death not associated with CTCAE term † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Weight gain † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Fatigue (asthenia, lethargy, malaise) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	4/6 (66.67%)	4	0/1 (0.00%)	0	0/1 (0.00%)	0	2/4 (50.00%)	2	2/3 (66.67%)	2	3/3 (100.00%)	3	3/4 (75.00%)	3	4/4 (100.00%)	4	2/6 (33.33%)	2
Rigors/chills † 1	1/1 (100.00%)	1	0/1 (0.00%)	0	3/6 (50.00%)	3	1/1 (100.00%)	1	0/1 (0.00%)	0	2/4 (50.00%)	2	1/3 (33.33%)	1	2/3 (66.67%)	2	3/4 (75.00%)	3	3/4 (75.00%)	3	1/6 (16.67%)	1
Sweating (diaphoresis) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	3/6 (50.00%)	3	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	1/3 (33.33%)	1	2/3 (66.67%)	2	2/4 (50.00%)	2	1/4 (25.00%)	1	1/6 (16.67%)	1
Weight loss † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	4/6 (66.67%)	4	0/1 (0.00%)	0	0/1 (0.00%)	0	3/4 (75.00%)	3	2/3 (66.67%)	2	0/3 (0.00%)	0	1/4 (25.00%)	1	1/4 (25.00%)	1	1/6 (16.67%)	1
Pain-Other (generalized pain) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Hepatobiliary disorders
Liver dysfunction/failure (clinical) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Pancreatitis † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	1/4 (25.00%)	1	0/6 (0.00%)	0
Immune system disorders
Cytokine release syndrome/acute infusion reaction † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	2/6 (33.33%)	2	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Allergic reaction/hypersensitivity (including drug fever) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Infections and infestations
Febrile neutropenia † 1 [1]	0/1 (0.00%)	0	1/1 (100.00%)	1	2/6 (33.33%)	2	0/1 (0.00%)	0	0/1 (0.00%)	0	4/4 (100.00%)	4	2/3 (66.67%)	2	3/3 (100.00%)	3	4/4 (100.00%)	4	4/4 (100.00%)	4	5/6 (83.33%)	5
Infection † 1	0/1 (0.00%)	0	1/1 (100.00%)	1	2/6 (33.33%)	2	1/1 (100.00%)	1	1/1 (100.00%)	1	3/4 (75.00%)	3	2/3 (66.67%)	2	1/3 (33.33%)	1	1/4 (25.00%)	1	1/4 (25.00%)	1	1/6 (16.67%)	1
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia) † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	6/6 (100.00%)	6	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	3/3 (100.00%)	3	3/3 (100.00%)	3	4/4 (100.00%)	4	4/4 (100.00%)	4	1/6 (16.67%)	1
Sodium, serum-high (hypernatremia) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Calcium, serum-high (hypercalcemia) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	1/4 (25.00%)	1	0/6 (0.00%)	0
Potassium, serum-low (hypokalemia) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	2/6 (33.33%)	2	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	2/4 (50.00%)	2	1/4 (25.00%)	1	0/6 (0.00%)	0
Alkaline phosphatase † 1	1/1 (100.00%)	1	0/1 (0.00%)	0	3/6 (50.00%)	3	1/1 (100.00%)	1	0/1 (0.00%)	0	4/4 (100.00%)	4	2/3 (66.67%)	2	1/3 (33.33%)	1	3/4 (75.00%)	3	4/4 (100.00%)	4	2/6 (33.33%)	2
Bilirubin (hyperbilirubinemia) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	1/1 (100.00%)	1	0/1 (0.00%)	0	3/4 (75.00%)	3	1/3 (33.33%)	1	1/3 (33.33%)	1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/6 (16.67%)	1
Creatinine † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	1/4 (25.00%)	1	3/4 (75.00%)	3	1/6 (16.67%)	1
Calcium, serum-low (hypocalcemia) † 1	1/1 (100.00%)	1	0/1 (0.00%)	0	5/6 (83.33%)	5	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	3/3 (100.00%)	3	3/3 (100.00%)	3	3/4 (75.00%)	3	2/4 (50.00%)	2	1/6 (16.67%)	1
Magnesium, serum-low (hypomagnesemia) † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	6/6 (100.00%)	6	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	3/3 (100.00%)	3	3/3 (100.00%)	3	2/4 (50.00%)	2	2/4 (50.00%)	2	0/6 (0.00%)	0
Phosphate, serum-low (hypophosphatemia) † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	6/6 (100.00%)	6	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	1/3 (33.33%)	1	3/3 (100.00%)	3	4/4 (100.00%)	4	3/4 (75.00%)	3	2/6 (33.33%)	2
Sodium, serum-low (hyponatremia) † 1	1/1 (100.00%)	1	1/1 (100.00%)	1	2/6 (33.33%)	2	0/1 (0.00%)	0	0/1 (0.00%)	0	3/4 (75.00%)	3	1/3 (33.33%)	1	3/3 (100.00%)	3	3/4 (75.00%)	3	1/4 (25.00%)	1	0/6 (0.00%)	0
AST, SGOT (serum glutamic oxaloacetic transaminase) † 1	0/1 (0.00%)	0	1/1 (100.00%)	1	3/6 (50.00%)	3	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	1/3 (33.33%)	1	2/3 (66.67%)	2	4/4 (100.00%)	4	4/4 (100.00%)	4	2/6 (33.33%)	2
ALT, SGPT (serum glutamic pyruvic transaminase) † 1	0/1 (0.00%)	0	1/1 (100.00%)	1	4/6 (66.67%)	4	1/1 (100.00%)	1	1/1 (100.00%)	1	4/4 (100.00%)	4	2/3 (66.67%)	2	2/3 (66.67%)	2	4/4 (100.00%)	4	4/4 (100.00%)	4	3/6 (50.00%)	3
Magnesium, serum-high (hypermagnesemia) † 1	0/1 (0.00%)	0	1/1 (100.00%)	1	2/6 (33.33%)	2	1/1 (100.00%)	1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Uric acid, serum-high (hyperuricemia) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Musculoskeletal and connective tissue disorders
Fracture † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1
Nervous system disorders
Memory impairment † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Hemorrhage, CNS † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Confusion † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	2/4 (50.00%)	2	0/6 (0.00%)	0
Dizziness † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	4/4 (100.00%)	4	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Mood alteration † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	2/6 (33.33%)	2	0/1 (0.00%)	0	1/1 (100.00%)	1	2/4 (50.00%)	2	1/3 (33.33%)	1	0/3 (0.00%)	0	1/4 (25.00%)	1	1/4 (25.00%)	1	0/6 (0.00%)	0
Psychosis (hallucinations/delusions) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Neuropathy:sensory † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1
Renal and urinary disorders
Hemorrhage, GU † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Renal failure † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	1/1 (100.00%)	1	1/1 (100.00%)	1	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Hiccoughs (hiccups, singultus) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0
Dyspnea (shortness of breath) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	2/6 (33.33%)	2	0/1 (0.00%)	0	0/1 (0.00%)	0	2/4 (50.00%)	2	0/3 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	2/4 (50.00%)	2	0/6 (0.00%)	0
Hypoxia † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
Cough † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	3/6 (50.00%)	3	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	2/3 (66.67%)	2	1/3 (33.33%)	1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/6 (16.67%)	1
Pericardial effusion (non-malignant) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Skin and subcutaneous tissue disorders
Dry skin † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	2/6 (33.33%)	2	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Hair loss/alopecia (scalp or body) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Rash/desquamation † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	3/6 (50.00%)	3	1/1 (100.00%)	1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/6 (33.33%)	2
Bruising (in absence of Grade 3 or 4 thrombocytopenia) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Hypopigmentation † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Pruritis/itching † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	2/6 (33.33%)	2	0/1 (0.00%)	0	1/1 (100.00%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	2/4 (50.00%)	2	0/4 (0.00%)	0	0/6 (0.00%)	0
Flushing † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1
Vascular disorders
Thrombosis/thrombus/embolism † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	1/6 (16.67%)	1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0
Vascular-Other (anasarca) † 1	0/1 (0.00%)	0	0/1 (0.00%)	0	0/6 (0.00%)	0	0/1 (0.00%)	0	0/1 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE (3.0); [1] (fever of unknown origin without clinically or microbiologically documented infection) (ANC <1.0x10e9/L, fever >=38.5 degrees C)

Limitations and Caveats

Due to the unexpected toxicities, likely attributable to the tumor infiltrating lymphocytes (TIL) transduced with IL-12, and low percentage of durable responses, we decided to close this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Steven Rosenberg
• Organization: National Cancer Institute
• Phone: 301-496-4164
• EMail: sar@mail.nih.gov

Publications of Results:

Zhang L, Morgan RA, Beane JD, Zheng Z, Dudley ME, Kassim SH, Nahvi AV, Ngo LT, Sherry RM, Phan GQ, Hughes MS, Kammula US, Feldman SA, Toomey MA, Kerkar SP, Restifo NP, Yang JC, Rosenberg SA. Tumor-infiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma. Clin Cancer Res. 2015 May 15;21(10):2278-88. doi: 10.1158/1078-0432.CCR-14-2085. Epub 2015 Feb 18.

Other Publications:

Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66.

Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul;17(7):2105-16. Review.

Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007 Feb 1;109(3):455-64. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kerkar SP, Goldszmid RS, Muranski P, Chinnasamy D, Yu Z, Reger RN, Leonardi AJ, Morgan RA, Wang E, Marincola FM, Trinchieri G, Rosenberg SA, Restifo NP. IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors. J Clin Invest. 2011 Dec;121(12):4746-57. doi: 10.1172/JCI58814. Epub 2011 Nov 7.

• Responsible Party: Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT01236573
• Other Study ID Numbers: 110011; 11-C-0011
• First Submitted: November 5, 2010
• First Posted: November 7, 2010
• Results First Submitted: August 20, 2015
• Results First Posted: October 26, 2015
• Last Update Posted: November 26, 2015