NCT02963831

A Study to Investigate ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 67 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Colorectal Cancer
• Ovarian Cancer
• Appendiceal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	ONCOS-102	ONCOS-102 was administered by intraperitoneal infusion at weekly intervals for 6 weeks.
DRUG	Durvalumab	Durvalumab was administered by IV infusion once every four weeks for a total of 10 (Cohort A) or 12 four-week cycles.
DRUG	Cyclophosphamide	A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.

Timeline

• Start date: 2017-09-07
• Primary completion: 2022-06-25
• Completion: 2022-06-25
• First posted: 2016-11-15
• Last updated: 2022-12-22
• Results posted: 2022-12-22

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study