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

NCT ID: NCT02963831

Last Updated: 2022-12-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

67 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-07

Study Completion Date

2022-06-25

Brief Summary

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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

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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

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Colorectal Cancer Ovarian Cancer Appendiceal Cancer

Keywords

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Oncos-102 Durvalumab Peritoneal Cyclophosphamide

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

The Phase 1 cohorts were enrolled sequentially. In Phase 2, the two expansion cohorts are enrolled in parallel.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A: ONCOS-102 Dose Escalation

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.

Group Type EXPERIMENTAL

ONCOS-102

Intervention Type BIOLOGICAL

ONCOS-102 was administered by intraperitoneal infusion at weekly intervals for 6 weeks.

Durvalumab

Intervention Type DRUG

Durvalumab was administered by IV infusion once every four weeks for a total of 10 (Cohort A) or 12 four-week cycles.

Cyclophosphamide

Intervention Type DRUG

A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.

Cohort B: ONCOS-102 Dose Escalation

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.

Group Type EXPERIMENTAL

ONCOS-102

Intervention Type BIOLOGICAL

ONCOS-102 was administered by intraperitoneal infusion at weekly intervals for 6 weeks.

Durvalumab

Intervention Type DRUG

Durvalumab was administered by IV infusion once every four weeks for a total of 10 (Cohort A) or 12 four-week cycles.

Cyclophosphamide

Intervention Type DRUG

A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.

Cohort 1: Epithelial Ovarian Cancer

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.

Group Type EXPERIMENTAL

ONCOS-102

Intervention Type BIOLOGICAL

ONCOS-102 was administered by intraperitoneal infusion at weekly intervals for 6 weeks.

Durvalumab

Intervention Type DRUG

Durvalumab was administered by IV infusion once every four weeks for a total of 10 (Cohort A) or 12 four-week cycles.

Cyclophosphamide

Intervention Type DRUG

A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.

Cohort 2: Metastatic Colorectal Cancer

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.

Group Type EXPERIMENTAL

ONCOS-102

Intervention Type BIOLOGICAL

ONCOS-102 was administered by intraperitoneal infusion at weekly intervals for 6 weeks.

Durvalumab

Intervention Type DRUG

Durvalumab was administered by IV infusion once every four weeks for a total of 10 (Cohort A) or 12 four-week cycles.

Cyclophosphamide

Intervention Type DRUG

A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.

Interventions

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ONCOS-102

ONCOS-102 was administered by intraperitoneal infusion at weekly intervals for 6 weeks.

Intervention Type BIOLOGICAL

Durvalumab

Durvalumab was administered by IV infusion once every four weeks for a total of 10 (Cohort A) or 12 four-week cycles.

Intervention Type DRUG

Cyclophosphamide

A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.

Intervention Type DRUG

Other Intervention Names

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Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (GM-CSF-encoding adenovirus) MEDI4736 Imfinzi® Cytoxan®

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research Institute, New York City

OTHER

Sponsor Role collaborator

MedImmune LLC

INDUSTRY

Sponsor Role collaborator

Targovax ASA

INDUSTRY

Sponsor Role collaborator

Ludwig Institute for Cancer Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Facility

San Diego, California, United States

Site Status

Research Facility

Miami, Florida, United States

Site Status

Research Facility

Buffalo, New York, United States

Site Status

Research Facility

New York, New York, United States

Site Status

Research Facility

Toledo, Ohio, United States

Site Status

Research Facility

Charlottesville, Virginia, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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LUD2015-008

Identifier Type: -

Identifier Source: org_study_id