Sapanisertib in Treating Patients With Stage IV or Recurrent Lung Cancer

• ClinicalTrials.gov Identifier: NCT02417701
• Recruitment Status: Completed
• First Posted: April 16, 2015
• Results First Posted: April 5, 2022
• Last Update Posted: April 5, 2022
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Recurrent Lung Squamous Cell Carcinoma; Stage IV Lung Squamous Cell Carcinoma AJCC v7
• Interventions: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sapanisertib
• Enrollment: 34

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Treatment (Sapanisertib)
Arm/Group Description	Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Sapanisertib: Given PO
Period Title: Overall Study
Started	34
Completed	34
Not Completed	0

Baseline Characteristics

Arm/Group Title		Treatment (Sapanisertib)
Arm/Group Description		Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Sapanisertib: Given PO
Overall Number of Baseline Participants		34
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	34 participants
		68.52; (46 to 89)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants
	Female	12 35.3%
	Male	22 64.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants
	Hispanic or Latino	2 5.9%
	Not Hispanic or Latino	29 85.3%
	Unknown or Not Reported	3 8.8%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants
	American Indian or Alaska Native	0 0.0%
	Asian	4 11.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	4 11.8%
	White	24 70.6%
	More than one race	0 0.0%
	Unknown or Not Reported	2 5.9%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	34 participants
		34 100.0%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (Complete Response [CR] + Partial Response [PR])
Description	Overall response rate (CR+PR) will be calculated separately for each cohort, including exact 95% confidence intervals. Duration of overall response and duration of stable disease will be calculated and summarized. Overall response rate was determined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	CT imaging was obtained after every 2 cycles, or 8 weeks, starting from cycle 1 day 1 until end of study treatment, up to 1 year.

Outcome Measure Data

Analysis Population Description

The number of participants analyzed for ORR is the response evaluable cohort as defined by the protocol, which is a subset of the total study population reflected in the participant flow module.

Arm/Group Title	NFEL2 Squamous Cohort	KEAP1 Squamous Cohort	KRAS/NFE2L2 or KEAP1 NSCLC Cohort
Arm/Group Description:	Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	12	6	6
Measure Type: Count of Participants; Unit of Measure: Participants
ORR: Complete Response + Partial Response	3 25.0%	1 16.7%	0 0.0%
No ORR	9 75.0%	5 83.3%	6 100.0%

2. Secondary Outcome

Title	Progression-free Survival
Description	Median progression-free survival will be estimated using the Kaplan-Meier method with a two-sided 95% confidence interval. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a unequivocal increase in a non-target lesion, or the appearance of new lesions
Time Frame	From start of treatment (cycle 1 day 1) until the date of first documented progression or death, over the trial enrollment period, up to 1 year.

Outcome Measure Data

Analysis Population Description

PFS in the secondary outcome section is the response evaluable cohort, which is a subset of the total study population.

Arm/Group Title	NFEL2 Squamous Cohort	KEAP1 Squamous Cohort	KRAS/NFE2L2 or KEAP1 NSCLC Cohort
Arm/Group Description:	Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	12	6	6
Median (95% Confidence Interval); Unit of Measure: months
	8.9 [1]; (5.6 to NA)	3.7 [1]; (1.8 to NA)	2.1 [1]; (1.6 to NA)

[1]

Upper limit was not reached due to insufficient number of participants with events

3. Secondary Outcome

Title	Feasibility of Reverse Phase Protein Array Analysis, Defined as the Ability to Procure Sufficient Quantity and Quality of Tumor Protein for Sample
Description	Single target signaling changes will be reported as percentages relative to the baseline pre-treatment tumor sample. Larger scale pathway changes will qualitatively represented through heatmaps.
Time Frame	Up to week 2

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Treatment (Sapanisertib)
Arm/Group Description:	Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Sapanisertib: Given PO
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Up to 1 year
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Treatment (Sapanisertib)
Arm/Group Description	Patients receive sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Sapanisertib: Given PO
All-Cause Mortality
	Treatment (Sapanisertib)
	Affected / at Risk (%)
Total	6/34 (17.65%)
Serious Adverse Events
	Treatment (Sapanisertib)
	Affected / at Risk (%)
Total	8/34 (23.53%)
Gastrointestinal disorders
Diarrhea †	3/34 (8.82%)
Mucositis †	3/34 (8.82%)
Investigations
Creatinine Increased †	2/34 (5.88%)
Metabolism and nutrition disorders
Anorexia †	2/34 (5.88%)
Dehydration †	3/34 (8.82%)
Hyperglycemia †	3/34 (8.82%)
Vascular disorders
Thromboembolic event †	3/34 (8.82%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Treatment (Sapanisertib)
	Affected / at Risk (%)
Total	30/34 (88.24%)
Gastrointestinal disorders
Diarrhea †	10/34 (29.41%)
Mucositis oral †	6/34 (17.65%)
Nausea †	6/34 (17.65%)
Vomiting †	5/34 (14.71%)
Flatulence †	3/34 (8.82%)
General disorders
Fatigue †	11/34 (32.35%)
Investigations
Weight loss †	8/34 (23.53%)
Platelet count decreased †	5/34 (14.71%)
Cholesterol high †	3/34 (8.82%)
Metabolism and nutrition disorders
Hyperglycemia †	21/34 (61.76%)
Anorexia †	9/34 (26.47%)
Hypertriglyceridemia †	5/34 (14.71%)
Respiratory, thoracic and mediastinal disorders
Cough †	5/34 (14.71%)
Dyspnea †	5/34 (14.71%)
Skin and subcutaneous tissue disorders
Rash maculo-papular †	8/34 (23.53%)
Pruritus †	6/34 (17.65%)
Dry skin †	5/34 (14.71%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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. Paul Paik, MD
• Organization: Memorial Sloan Kettering Cancer Center
• Phone: 646-608-3759
• EMail: paikp@mskcc.org

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02417701
• Other Study ID Numbers: NCI-2015-00545; NCI-2015-00545 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 15-249; 2015-00500; 9780 ( Other Identifier: Memorial Sloan Kettering Cancer Center ); 9780 ( Other Identifier: CTEP ); P30CA008748 ( U.S. NIH Grant/Contract )
• First Submitted: April 14, 2015
• First Posted: April 16, 2015
• Results First Submitted: January 20, 2022
• Results First Posted: April 5, 2022
• Last Update Posted: April 5, 2022