Clinical trial NCT02963831: A Study to Investigate 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Ovarian Cancer
Appendiceal Cancer
Keywords: Oncos-102
Durvalumab
Peritoneal
Cyclophosphamide
Lead sponsor: Ludwig Institute for Cancer Research
Sponsor class: OTHER
Collaborators: name: Cancer Research Institute, New York City
name: MedImmune LLC
name: Targovax ASA
First posted: 2016-11-15
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The Phase 1 cohorts were enrolled sequentially. In Phase 2, the two expansion cohorts are enrolled in parallel.
Primary purpose: TREATMENT

Brief summary: This is a two-part Phase 1/2 dose escalation and dose expansion study of an Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (GM-CSF-encoding adenovirus), ONCOS-102, in combination with anti-programmed death ligand-1 (PD-L1) antibody, durvalumab, in adult subjects with peritoneal disease who have failed prior standard chemotherapy and have histologically confirmed epithelial ovarian cancer or metastatic colorectal cancer.

Detailed description: ONCOS-102 will be administered intraperitoneally (IP) at weekly intervals for 6 weeks.

A bolus dose of 300 mg cyclophosphamide (CPO) will be administered intravenously (IV) 1 to 3 days before the first infusion of ONCOS-102. Durvalumab will be administered by IV infusion once every four weeks (Q4W) for a total of 12 four-week cycles.

Phase 1 of the study is a dose escalation phase, which will use a 3+3 design to evaluate the safety of ONCOS-102 monotherapy before initiation of durvalumab and to identify the recommended combination dose (RCD) of a fixed dose of durvalumab (1500 mg) + ONCOS-102 at 2 dose levels (1 x 10\^11 viral particles (VPs) and 3 x 10\^11 VPs).

Subjects treated at the RCD of 3 x 10\^11 VPs ONCOS-102 will be included in the Phase 2 expansion cohort based on their tumor diagnosis.

Phase 2 of the study is the dose expansion phase, which will further explore the safety and anti-tumor activity for the RCD in 2 expansion cohorts with peritoneal disease:

1. Epithelial ovarian cancer
2. Metastatic colorectal cancer

Simon's 2-Stage MINIMAX Design will be used in Phase 2 for Expansion Cohorts 1 and 2. In the first stage, 18 subjects will be enrolled in Cohort 1 and 13 subjects in Cohort 2 (including the 6 subjects at the RCD from the dose escalation phase).

If 5 or more subjects in Cohort 1, or one or more subjects in Cohort 2, demonstrate clinical benefit (defined as percentage of subjects who are not in progression at end of Week 24), 15 additional subjects will be enrolled in Stage 2 of Cohort 1, and 14 additional subjects will be enrolled in Stage 2 of Cohort 2.

The primary endpoint is the percentage of subjects who are not in progression at the end of Week 24 as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).

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 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.

Primary outcomes:
measure: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Dose Limiting Toxicities (DLTs)
timeFrame: up to 31 months (90 days after the last dose of study medication).
measure: Progression-free Survival (PFS) at Week 24 as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Median Progression-free Survival (PFS) as Measured by Response Evaluation in Solid Tumors 1.1 (RECIST 1.1) Using Kaplan-Meier Method
timeFrame: Up to 29 months
measure: Objective Response Rate as Measured by as Measured by Response Evaluation in Solid Tumors 1.1 (RECIST 1.1)
timeFrame: Up to 15 months
measure: Progression-free Survival (PFS) at Week 24 as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
timeFrame: Up to 24 Weeks
measure: Median Progression-free Survival (PFS) by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method
timeFrame: Up to 39 months
measure: Objective Response Rate as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
timeFrame: Up to 15 months
measure: Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method
timeFrame: Up to 39 months
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Research Facility
state: California
city: Miami
country: United States
facility: Research Facility
state: Florida
city: Buffalo
country: United States
facility: Research Facility
state: New York
city: New York
country: United States
facility: Research Facility
state: New York
city: Toledo
country: United States
facility: Research Facility
state: Ohio
city: Charlottesville
country: United States
facility: Research Facility
state: Virginia
Study officials:
References: