A Study to Evaluate the Safety of Intuvax Administered Intra-tumorally in Patients With Gastrointestinal Stromal Tumors (GIST)

• ClinicalTrials.gov Identifier: NCT02686944
• Recruitment Status: Completed
• First Posted: February 22, 2016
• Last Update Posted: July 5, 2019
• Sponsor: Immunicum AB
• Information provided by (Responsible Party): Immunicum AB

Tracking Information

• First Submitted Date: January 19, 2016
• First Posted Date: February 22, 2016
• Last Update Posted Date: July 5, 2019
• Actual Study Start Date: June 1, 2016
• Actual Primary Completion Date: May 10, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 23, 2018)

• Changes in vital signs (heart rate, blood pressure, body temperature) [ Time Frame: Up to 12 months after vaccination 1 ]
• Changes in lab parameters (hematology and biochemistry) during the study versus baseline [ Time Frame: Up to 12 months after vaccination 1 ]
• Adverse events according to CTCAE v 4.03 [ Time Frame: Up to 12 months after vaccination 1 ]

Original Primary Outcome Measures (submitted: February 16, 2016)

• Changes in vital signs (heart rate, blood pressure, body temperature) [ Time Frame: Within 6 hours after each vaccination of Intuvax and at 3 and 6 months versus baseline ]
• Changes in lab parameters (biochemistry, haematology) [ Time Frame: Just before vaccination 1, at 14 days after vaccination 1, at 28 days after vaccination 2, at 3 and 6 months after vaccination 1 ]
• Adverse events [ Time Frame: At time of vaccination 1 and through study completion, an average of 6 months ]
• Changes in lab parameters (coagulation) [ Time Frame: Just before vaccination 1, at 14 days after vaccination 1 and at 28 days after vaccination 2 ]

Current Secondary Outcome Measures (submitted: February 23, 2018)

• Tumor response by determining changes (PD, SD, PR, CR) in tumor diameter according to mRECIST [ Time Frame: Every 3 months up to 12 months after vaccination 1 ]
  Criteria based on the diameter of the contrast-enhanced portions of the tumor
• Tumor response by determining changes (PD, SD, PR, CR) in tumor diameter according to RECIST 1.1. [ Time Frame: Every 3 months up to 12 months after vaccination 1 ]
  Criteria based on the maximal tumor diameter
• Tumor response by determining changes (PD, SD, PR, CR) in tumor diameter according to Choi criteria [ Time Frame: Every 3 months up to 12 months after vaccination 1 ]
  Criteria based on unidimensional tumor size and tumor density on contrast-enhanced CT images.
• Progression free survival according to mRECIST [ Time Frame: Up to 12 months after vaccination 1 ]
  Criteria based on the diameter of the contrast-enhanced portions of the tumor
• Progression free survival according to RECIST 1.1 [ Time Frame: Up to 12 months after vaccination 1 ]
  Criteria based on the maximal tumor diameter
• Progression free survival according to Choi criteria [ Time Frame: Up to 12 months after vaccination 1 ]
  Criteria based on unidimensional tumor size and tumor density on contrast-enhanced CT images.
• Changes in WHO-ECOG score [ Time Frame: Up to 12 months after vaccination 1 ]
• Levels of autoimmunization parameters [ Time Frame: Up to 3 months after vaccination 1 ]
  Screening of autoantibodies against nuclear antigens (ANA), including the nuclear antigens SSA, SSB, Sm, RNP, Scl-70, Centromeres and Jo-1
• Levels of alloimmunization parameters [ Time Frame: Up to 3 months after vaccination 1 ]
  Screening of alloantibodies against HLA-A, B, C (MHC-class I) and HLA-DR (MHC-class II) antigens

Original Secondary Outcome Measures (submitted: February 16, 2016)

• Tumor response by determining changes (PD, SD, PR, CR) in tumor diameter according to mRECIST [ Time Frame: Within 2 weeks of vaccination 1 and at 3 and 6 months after vaccination 1 ]
  Criteria based on the diameter of the contrast-enhanced portions of the tumor
• Tumor response by determining changes (PD, SD, PR, CR) in tumor diameter according to RECIST 1.1. [ Time Frame: Within 2 weeks of vaccination 1 and at 3 and 6 months after vaccination 1 ]
  Criteria based on the maximal tumor diameter
• Tumor response by determining changes (PD, SD, PR, CR) in tumor diameter according to Choi criteria [ Time Frame: Within 2 weeks of vaccination 1 and at 3 and 6 months after vaccination 1 ]
  Criteria based on unidimensional tumor size and tumor density on contrast-enhanced CT images.
• Progression free survival according to mRECIST [ Time Frame: Within 2 weeks of vaccination 1 and at 3 and 6 months after vaccination 1 ]
  Criteria based on the diameter of the contrast-enhanced portions of the tumor
• Progression free survival according to RECIST 1.1 [ Time Frame: Within 2 weeks of vaccination 1 and at 3 and 6 months after vaccination 1 ]
  Criteria based on the maximal tumor diameter
• Progression free survival according to Choi criteria [ Time Frame: Within 2 weeks of vaccination 1 and at 3 and 6 months after vaccination 1 ]
  Criteria based on unidimensional tumor size and tumor density on contrast-enhanced CT images.
• Changes in WHO-ECOG score [ Time Frame: At 3 and 6 months versus baseline ]
• Levels of autoimmunization parameters [ Time Frame: Within 2 weeks of vaccination and at 3 months after vaccination 1 ]
  Screening of autoantibodies against nuclear antigens (ANA), including the nuclear antigens SSA, SSB, Sm, RNP, Scl-70, Centromeres and Jo-1
• Levels of alloimmunization parameters [ Time Frame: Within 2 weeks of vaccination and at 3 months after vaccination 1 ]
  Screening of alloantibodies against HLA-A, B, C (MHC-class I) and HLA-DR (MHC-class II) antigens

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety of Intuvax Administered Intra-tumorally in Patients With Gastrointestinal Stromal Tumors
• Official Title: A Phase I Open-label Study Evaluating Safety and Efficacy of Intratumorally Administered Intuvax in Patients With Progressing Gastrointestinal Stromal Tumors (GIST) During Ongoing Second, Third or Fourth Line Treatment With Tyrosine Kinase Inhibition Therapy. A Prospective Single Armed, Open Label Phase I Safety and Efficacy Study
• Brief Summary: The study is a prospective single armed, open label phase I study. Patients with advanced or metastatic GIST and tumor progression despite ongoing treatment with second, third or fourth line TKI treatment, and with at least one measureable tumor lesion, will be eligible for the study. A maximum of 12 patients will be included in this study. The patients will continue with TKI treatment until the 3 months follow up visit. If further tumor progression TKI will be withdrawn but if stable disease or objective response the patient will continue with TKI until progress. The investigational product Intuvax will be injected into a tumor lesion at two or three treatment occasions; day 1, 14 days (±3 days) after the first vaccination, and 28 days (±3 days) after the second vaccination (patient 7-12 only). Intuvax will be injected in a viable part of the tumor, using ultrasound-guided or CT technique for correct administration.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:

Open Label

Primary Purpose: Treatment

• Condition: Gastrointestinal Stromal Tumor

Intervention

Biological: Intuvax (ilixadencel)

Therapeutic vaccine: allogeneic, proinflammatory dendritic cells, suspension for intratumoral injection

Other Name: ilixadencel

Study Arms

Experimental: Intuvax (ilixadencel)

Intuvax (ilixadencel) will be administered 2 or 3 times. First injection Day 1 (pat 1-12), second injection 14 days after the first vaccination (pat 1-12), third injection 28 days after the second vaccination (only pat 7-12).

Max 10 000 000 allogeneic dendritic cells/ml per injection.

Intervention: Biological: Intuvax (ilixadencel)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 3, 2019): 6
• Original Estimated Enrollment (submitted: February 16, 2016): 12
• Actual Study Completion Date: May 10, 2019
• Actual Primary Completion Date: May 10, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Be informed of the nature of the study and have provided written informed consent.
2. At least 18 years of age.
3. Diagnosis of GIST (according to modified NIH criteria, 2011) where curative excision is no longer an option, i.e. confirmed unresectable or metastatic GIST, and that has progressed on second, third or fourth line tyrosine kinase inhibitor (TKI) treatment.
4. Radiologically measurable tumor(s), i.e at least 3 cm in longest uni-dimensional diameter as measured by CT
5. Clinical and/or CT verified disease progression despite ongoing second, third or fourth line treatment with a TKI
6. Female who has been post-menopausal for more than one (1) year or female of childbearing potential using a highly efficient method of contraception (i.e. a method with less than 1% failure rate [e.g. sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner with combined use of condom and/or birth control pills]) during study participation. Female of childbearing potential must have a negative blood pregnancy test at Screening, and if randomized to vaccination a negative blood or urine pregnancy test within one (1) day before each dose of Intuvax, or Male agreeing to use condoms during the study participation or male having a female partner who is using a highly efficient method of contraception as described above during the partner's study participation.

Exclusion Criteria:

1. Performance status > ECOG 2
2. Known major reaction/adverse event in connection with previously made vaccination (e.g. asthma, anaphylaxia or other serious reaction)
3. Known major reaction/adverse event in connection with previous transfusions of blood products
4. Active autoimmune disease requiring treatment with systemic immunosuppressive agents, e.g. inflammatory bowel disease, multiple sclerosis, sarcoidosis, psoriasis, autoimmune hemolytic anemia, rheumatoid arthritis, SLE, vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other rheumatological diseases.
5. Tested positive for HIV
6. Active virus disease (HBV and HCV).
7. Ongoing infection that requires treatment with parenteral antibiotics or antiviral medication
8. Corticosteroid treatment per os exceeding 10mg/day within 7 days prior to the first injection of Intuvax. Inhaled, intranasal and local steroids accepted.

9. Inadequate laboratory parameters, i.e.:

   • B-Leukocyte count < 3.0 x109/L
   • B-Platelet count < 75 x109/L
   • B-Hemoglobin < 100 g/L
   • P-Prothrombincomplex (PK) >1.4
   • P-APT time outside normal limit
10. Previous organ transplantation
11. Pregnant or lactating women
12. Life expectancy less than 3 months.
13. Investigational treatment (within 28 days) prior to the first injection of Intuvax
14. Known blood dyscrasia (bleeding complication)
15. Prior history of invasive cancer within 5 years before screening, except for adequately treated in situ carcinomas or non melanoma skin cancer
16. History of alcohol or substance abuse
17. patient will not be available for follow up assessments
18. Any other reason that, in the opinion of the investigator, contraindicates that the patient participates in the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT02686944
• Other Study ID Numbers: IM-103; 2015-002689-22 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Immunicum AB
• Study Sponsor: Immunicum AB
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; Immunicum AB

• PRS Account: Immunicum AB
• Verification Date: July 2019