Study of DPX-Survivac Therapy in Patients With Recurrent Ovarian Cancer

A Phase 1b/2 Study of an Immunotherapeutic Vaccine, DPX-Survivac With Low Dose Cyclophosphamide and Epacadostat (INCB024360) in Patients With Recurrent Ovarian Cancer

T cell activating therapy DPX-Survivac, low dose oral cyclophosphamide, and IDO1 inhibitor epacadostat will be tested together for the first time in patients with recurrent ovarian, fallopian tube, or peritoneal cancer to determine the safety and potential immune-modulating activity of the combination of these agents.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent Fallopian Tube Cancer; Recurrent Epithelial Ovarian Cancer; Recurrent Peritoneal Cancer
• Intervention / Treatment: Other: DPX-Survivac; Drug: Cyclophosphamide; Drug: Epacadostat (INCB024360)

Detailed Description

The Phase 1b component is a multicenter, non-randomized, open label, uncontrolled, safety and effectiveness study to identify the recommended Phase 2 dose (R2PD) of epacadostat in combination with DPX-Survivac and cyclophosphamide.

The Phase 2 component was initially a multicenter, randomized, open-label study to evaluate the safety and effectiveness of DPX-Survivac + cyclophosphamide with or without the RP2D of epacadostat. The design of the study has been amended to a single arm study in which up to 16 evaluable subjects will be enrolled to received DPX-Survivac plus intermittent low dose cyclophosphamide (i.e. treatment arm 2).

• Study Type: Interventional
• Enrollment (Anticipated): 85
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Tom Baker Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montréal, Quebec, Canada, H2X 3E4
      • Centre hospitalier de l'Université de Montréal (CHUM)
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • New York
    • New York, New York, United States, 10028
      • Lenox Hill Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University, Knight Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Key Inclusion Criteria:

• Histologically confirmed, stage IIc-IV epithelial ovarian, fallopian tube or peritoneal cancer
• Platinum-resistant or -sensitive subjects after completing first-line treatment (debulking surgery and adjuvant or neoadjuvant treatment with standard of care treatment such as carboplatin and paclitaxel). Subjects may have had any number of subsequent lines of chemotherapy.
• Must have evidence of progressive disease with either biochemical (i.e. rising CA-125) and/or radiologic progression
• Must have measurable disease by RECIST v1.1, a successful pre-treatment tumor biopsy, and be willing to undergo tumor biopsy during treatment
• Ambulatory with an ECOG 0-1
• Life expectancy ≥ 6 months
• Meet protocol-specified laboratory requirements

Key Exclusion Criteria:

• Eligible for otherwise curative treatment or undergoing concurrent therapy
• Prior receipt of survivin based vaccines or immune checkpoint inhibitors (e.g. anti-CTLA-4, anti-PD-1, anti-PD-L1, or any other antibody or drug specifically targeting T cell co-stimulation) or an IDO inhibitor
• Concurrent second malignancy other than non-melanoma skin cancer, cervical carcinoma in situ, or controlled bladder cancer
• Clinical ascites
• Any single lesion greater than or equal to 4 cm (per RECIST v1.1)
• Malignant bowel obstruction
• History of autoimmune disease requiring treatment within the last two years (except vitiligo or diabetes)
• Recent history of thyroiditis
• Presence of a serious acute infection or chronic infection
• Active central nervous system (CNS) or leptomeningeal metastasis (brain metastases)
• GI condition that might limit absorption of oral agents
• Other serious intercurrent chronic or acute illness, including myocardial infarction or cerebrovascular event within 6 months
• Ongoing treatment with steroid therapy or other immunosuppressive
• Receipt of monoamine oxidase inhibitors (MAOIs) or UGT1A9 inhibitors
• Receipt of live attenuated vaccines
• Acute or chronic skin and/or microvascular disorders
• Edema or lymphedema in the lower limbs > grade 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; DPX-Survivac, Cyclophosphamide, Epacadostat (Phase 1 and initially Phase 2)	Other: DPX-Survivac; SubQ injection; Drug: Cyclophosphamide; PO BID; Drug: Epacadostat (INCB024360); PO BID
Experimental: Arm 2; DPX-Survivac, Cyclophosphamide (in Phase 2 only)	Other: DPX-Survivac; SubQ injection; Drug: Cyclophosphamide; PO BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as measured by adverse event reporting (CTCAE)		up to 13 months
Objective Response Rate (Phase 2 only)	Evaluated using modified RECIST v1.1	up to 13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (for each treatment group)	Evaluated using modified RECIST v1.1	up to 13 months
Duration of Response		up to 13 months
Cell mediated immunity as measured by the antigen specific response in peripheral blood		bimonthly for up to 13 months
Evaluation of treatment-induced changes in tumor infiltrating lymphocytes		at 8 to 10 weeks
Time to Progression		up to 13 months
Overall Survival		up to 13 months

Collaborators and Investigators

• Sponsor: ImmunoVaccine Technologies, Inc. (IMV Inc.)
• Collaborators: Incyte Corporation

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): October 1, 2020
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: May 18, 2016
• First Submitted That Met QC Criteria: May 24, 2016
• First Posted (Estimate): May 27, 2016

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; ovarian; fallopian tube; recurrent; tumor; T cell activation; peritoneal; measurable
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Recurrence; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: ONC-DPX-Survivac-06; DeCidE1 (Other Identifier: Sponsor)