A Phase 1/2 Study to Investigate the Safety, Biologic and Anti-tumor Activity of ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies

• ClinicalTrials.gov Identifier: NCT02963831
• Recruitment Status: Recruiting
• First Posted: November 15, 2016
• Last Update Posted: February 23, 2021
• Sponsor: Ludwig Institute for Cancer Research
• Collaborators: Cancer Research Institute, New York City; MedImmune LLC; Targovax ASA
• Information provided by (Responsible Party): Ludwig Institute for Cancer Research

Tracking Information

• First Submitted Date: November 10, 2016
• First Posted Date: November 15, 2016
• Last Update Posted Date: February 23, 2021
• Actual Study Start Date: September 7, 2017
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2019)

Number of Adverse Events [ Time Frame: up to 15 months ]

Clinical laboratory tests, vital sign and weight measurements, physical exams, performance status evaluation, imaging scans and any other medically indicated assessments, including subject interviews, will be performed to detect new abnormalities and deteriorations of any pre-existing conditions. The investigator will evaluate any laboratory abnormalities for clinical significance, and clinically significant abnormalities will be recorded as adverse events. All clinically significant abnormalities and deteriorations from time of signing the informed consent to the end of study visit will be recorded in the Case Report Forms as adverse events and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

Original Primary Outcome Measures (submitted: November 10, 2016)

Number of Adverse Events [ Time Frame: up to 24 weeks ]

Clinical laboratory tests, vital sign and weight measurements, physical exams, performance status evaluation, imaging scans and any other medically indicated assessments, including subject interviews, will be performed to detect new abnormalities and deteriorations of any pre-existing conditions. The investigator will evaluate any laboratory abnormalities for clinical significance, and clinically significant abnormalities will be recorded as adverse events. All clinically significant abnormalities and deteriorations from time of signing the informed consent to the end of study visit will be recorded in the Case Report Forms as adverse events and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

Current Secondary Outcome Measures (submitted: October 20, 2020)

• Clinical Benefit (Complete Response, Partial Response and Stable Disease) for Cohorts 1 & 2 [ Time Frame: up to 24 weeks ]
  Clinical Benefit is defined as percentage of subjects who are in the study and not in progression at the end of Week 24.
• Objective Response Rate for Cohorts 1 & 2 [ Time Frame: up to 15 months ]
• Progression-free survival for Cohorts 1 & 2 [ Time Frame: Up to 15 months ]
• Overall Survival for Cohorts 1 & 2 [ Time Frame: up to 4 years ]

Original Secondary Outcome Measures (submitted: November 10, 2016)

• Clinical Benefit (CR, PR and SD) [ Time Frame: up to 24 weeks ]
• Objective Response Rate [ Time Frame: a least 4 weeks ]
• Progression-free survival [ Time Frame: up to 4 years ]
• Overall Survival [ Time Frame: up to 4 years ]

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

Descriptive Information

• Brief Title: A Phase 1/2 Study to Investigate the Safety, Biologic and Anti-tumor Activity of ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies
• Official Title: A Phase 1/2 Dose Escalation Study With Expansion Cohorts to Investigate the Safety, Biologic and Anti-tumor Activity of ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies
• Brief Summary: This is a two-part Phase 1/2 dose escalation and dose expansion study of the GMCSF-encoding adenovirus, ONCOS-102, in combination with anti-programmed death ligand-1 (PDL1) antibody, durvalumab, in adult subjects with peritoneal disease who have failed prior standard chemotherapy and have histologically confirmed platinum-resistant or refractory epithelial ovarian cancer or colorectal cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Colorectal Cancer
• Platinum-resistant Ovarian Cancer
• Appendiceal Cancer

Intervention

• Biological: ONCOS-102
  ONCOS-102 will be administered intraperitoneally infusion at weekly intervals for 6 weeks.
• Drug: Durvalumab
  Durvalumab will be administered by IV infusion once every four weeks for a total of 12 four-week cycles.
  Other Name: MEDI4736

Study Arms

• Experimental: Dose Escalation

  During Phase 1 of the study, subjects will be evaluated for DLTs before proceeding to a subsequent cohort. Dose escalation for the determination of RCD will be performed based on the available dose levels and the respective rules for a standard 3 + 3 dose escalation study design.

  For Cohort A, ONCOS-102 will be given as monotherapy the first six weeks, and then durvalumab (1500 mg) will be starting on day 71.

  For Cohorts B and C, ONCOS-102 will be administered for a total of 6 weeks while durvalumab will be given for a total of 12 four-week cycles.

  Interventions:

  • Biological: ONCOS-102
  • Drug: Durvalumab
• Experimental: Cohort 1: Platinum-resistant epithelial ovarian cancer
  ONCOS-102 will be administered for a total of 6 weeks, while durvalumab will be administered for a total of 12 cycles, starting on Day 15.
  Interventions:

  • Biological: ONCOS-102
  • Drug: Durvalumab
• Experimental: Cohort 2: Colorectal cancer
  ONCOS-102 will be administered for a total of 6 weeks, while durvalumab will be administered for a total of 12 cycles, starting on Day 15.
  Interventions:

  • Biological: ONCOS-102
  • Drug: Durvalumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 10, 2016): 78
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Subjects with peritoneal disease who have failed prior standard chemotherapy and have histologic confirmation of epithelial ovarian cancer or metastatic colorectal cancer (CRC) including cancer originating from the appendix.
2. Subject is willing to undergo a core needle biopsy during screening and Cycle 2, Study Week 5. Archival tumor samples are requested, but are not required for eligibility.
3. Previously treated for advanced cancer with no additional therapy options available known to prolong survival.
4. Laboratory parameters for vital functions should be in the normal range or not clinically significant.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion Criteria:

1. Treatment with an investigational agent within 4 weeks of starting study treatment or prior treatment with a checkpoint inhibitor (cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) antibodies).
2. Subject has known active central nervous system metastasis, glioma and nervous system malignancies including carcinomatous meningitis. Subjects with asymptomatic brain metastases or spinal cord compression who have been treated, are considered stable, and who have not received corticosteroids or anticonvulsants for at least 28 days prior to screening may be included. Subject has other active malignancy.
3. Known immunodeficiency or known to have evidence of acute or chronic or human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C or other uncontrolled inter-current illnesses.
4. Ongoing bowel perforation or presence of bowel fistula or abscess or history of small or large bowel obstruction within 3 months of registration, including subjects with palliative gastric drainage catheters. Subjects with palliative diverting ileostomy or colostomy are allowed if they have been symptom-free for more than 3 months.
5. Subjects with clinically significant cardiovascular disease, history of organ transplant or allogeneic bone marrow transplant, active known or history of autoimmune disease that might recur or major surgery within 28 days prior to the first dose or still recovering from prior surgery.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Mary Macri; 212-450-1515; clintrialinformation@licr.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02963831
• Other Study ID Numbers: LUD2015-008
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: Ludwig Institute for Cancer Research
• Study Sponsor: Ludwig Institute for Cancer Research

Collaborators

• Cancer Research Institute, New York City
• MedImmune LLC
• Targovax ASA

• Investigators: Not Provided
• PRS Account: Ludwig Institute for Cancer Research
• Verification Date: February 2021