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

Ludwig Institute for Cancer Research

Status and phase

Completed

Phase 2

Phase 1

Conditions

Appendiceal Cancer

Ovarian Cancer

Colorectal Cancer

Treatments

Drug: Cyclophosphamide

Drug: Durvalumab

Biological: ONCOS-102

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02963831

LUD2015-008

Details and patient eligibility

About

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.

Full 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:

Epithelial ovarian cancer
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).

Enrollment

67 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.
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.
Previously treated for advanced cancer with no additional therapy options available known to prolong survival.
Laboratory parameters for vital functions should be in the normal range or not clinically significant.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

Exclusion criteria

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).
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.
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.
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.
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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

67 participants in 4 patient groups

Cohort A: ONCOS-102 Dose Escalation

Experimental group

Description:

ONCOS-102, 1 x 10\^11 viral particles (VPs) monotherapy for 6 weeks, followed by durvalumab 1500 mg starting on Day 71. A bolus dose of 300 mg cyclophosphamide (CPO) was administered intravenously (IV) 1 to 3 days before the first infusion of ONCOS-102. ONCOS-102 was infused intraperitoneally (IP) in a total volume of 500 mL saline (0.9 mg/mL sodium chloride \[NaCl\] in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1. Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose every 4 weeks (Q4W) for 10 cycles, starting on Day 71. Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better.

Treatment:

Biological: ONCOS-102

Drug: Durvalumab

Drug: Cyclophosphamide

Cohort B: ONCOS-102 Dose Escalation

Experimental group

Description:

ONCOS-102, 1 x 10\^11 VPs + durvalumab 1500 mg starting on Day 15. A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102. ONCOS-102 was infused IP in a total volume of 500 mL saline (0.9 mg/mL NaCl in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1. Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose Q4W for 12 cycles, starting on Day 15. Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better.

Treatment:

Biological: ONCOS-102

Drug: Durvalumab

Drug: Cyclophosphamide

Cohort 1: Epithelial Ovarian Cancer

Experimental group

Description:

ONCOS-102, 3 x 10\^11 VPs + durvalumab 1500 mg starting on Day 15. A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102. ONCOS-102 was infused IP in a total volume of 500 mL saline (0.9 mg/mL NaCl in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1. Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose Q4W for 12 cycles, starting on Day 15. Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better.

Treatment:

Biological: ONCOS-102

Drug: Durvalumab

Drug: Cyclophosphamide

Cohort 2: Metastatic Colorectal Cancer

Experimental group

Description:

Treatment:

Biological: ONCOS-102

Drug: Durvalumab

Drug: Cyclophosphamide

Trial documents