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

NCT02963831 | Completed Phase 1 Results FDA Drug

• 1 other identifier: LUD2015-008
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 6

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.

Conditions

Colorectal Cancer; Ovarian Cancer; Appendiceal Cancer

Keywords

Oncos-102; Durvalumab; Peritoneal; Cyclophosphamide

Outcome Measures

Primary Outcomes (2)

• Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Dose Limiting Toxicities (DLTs)

  All Adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 19.0 and classified by MedDRA system organ class (SOC) and preferred term. The severity of AEs was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 90 days after the last dose of study treatment. TEAEs are those that occurred or worsened after administration of the first dose of study treatment. Deaths within the AE Reporting Period included all deaths that occurred during the study treatment period, or up to 90 days after the administration of the last dose of study drug or initiation of a new treatment.

  up to 31 months (90 days after the last dose of study medication).

• Progression-free Survival (PFS) at Week 24 as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up starting 8 weeks after the last disease assessment. Per RECIST 1.1, target lesions were categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria. PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression does not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the development of new lesions.

  Up to 24 weeks

Secondary Outcomes (6)

• Median Progression-free Survival (PFS) as Measured by Response Evaluation in Solid Tumors 1.1 (RECIST 1.1) Using Kaplan-Meier Method

  Up to 29 months

• Objective Response Rate as Measured by as Measured by Response Evaluation in Solid Tumors 1.1 (RECIST 1.1)

  Up to 15 months

• Progression-free Survival (PFS) at Week 24 as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

  Up to 24 Weeks

• Median Progression-free Survival (PFS) by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method

  Up to 39 months

• Objective Response Rate as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

  Up to 15 months

Study Arms (4)

Cohort A: ONCOS-102 Dose Escalation

EXPERIMENTAL

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.

Biological: ONCOS-102; Drug: Durvalumab; Drug: Cyclophosphamide

Cohort B: ONCOS-102 Dose Escalation

EXPERIMENTAL

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.

Biological: ONCOS-102; Drug: Durvalumab; Drug: Cyclophosphamide

Cohort 1: Epithelial Ovarian Cancer

EXPERIMENTAL

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.

Biological: ONCOS-102; Drug: Durvalumab; Drug: Cyclophosphamide

Cohort 2: Metastatic Colorectal Cancer

EXPERIMENTAL

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.

Biological: ONCOS-102; Drug: Durvalumab; Drug: Cyclophosphamide

Interventions

ONCOS-102 BIOLOGICAL

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

Also known as: Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (GM-CSF-encoding adenovirus)

Cohort 1: Epithelial Ovarian Cancer; Cohort 2: Metastatic Colorectal Cancer; Cohort A: ONCOS-102 Dose Escalation; Cohort B: ONCOS-102 Dose Escalation

Durvalumab DRUG

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

Also known as: MEDI4736, Imfinzi®

Cohort 1: Epithelial Ovarian Cancer; Cohort 2: Metastatic Colorectal Cancer; Cohort A: ONCOS-102 Dose Escalation; Cohort B: ONCOS-102 Dose Escalation

Cyclophosphamide DRUG

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

Also known as: Cytoxan®

Cohort 1: Epithelial Ovarian Cancer; Cohort 2: Metastatic Colorectal Cancer; Cohort A: ONCOS-102 Dose Escalation; Cohort B: ONCOS-102 Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• Cancer Research Institute, New York City: collaborator
• MedImmune LLC: collaborator
• Targovax ASA: collaborator

Study Sites (6)

Research Facility

San Diego, California, 92093-0698, United States

Location

Research Facility

Miami, Florida, 33136, United States

Location

Research Facility

Buffalo, New York, 14263, United States

Location

Research Facility

New York, New York, 10065, United States

Location

Research Facility

Toledo, Ohio, 43614, United States

Location

Research Facility

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Ovarian Neoplasms; Appendiceal Neoplasms

Interventions

durvalumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Cecal Neoplasms; Cecal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Jonathan Skipper
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The Phase 1 cohorts were enrolled sequentially. In Phase 2, the two expansion cohorts are enrolled in parallel.

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: November 15, 2016
• Study Start: September 7, 2017
• Primary Completion: June 25, 2022
• Study Completion: June 25, 2022
• Last Updated: December 22, 2022
• Results First Posted: December 22, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)