Study of an Immunotherapeutic, DPX-Survivac, in Combination With Low Dose Cyclophosphamide & Pembrolizumab, in Subjects With Selected Advanced & Recurrent Solid Tumors

A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment, DPX-Survivac in Combination With Low Dose Cyclophosphamide and Pembrolizumab, in Subjects With Selected Advanced and Recurrent Solid Tumours.

This study will assess the safety and efficacy of DPX-Survivac and low dose cyclophosphamide with pembrolizumab in subjects with selected advanced and recurrent solid tumours.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma; Ovarian Cancer; Bladder Cancer; Non-small Cell Lung Cancer; Microsatellite Instability-High
• Intervention / Treatment: Other: DPX-Survivac; Drug: Cyclophosphamide; Drug: Pembrolizumab

Detailed Description

This study is a Phase 2 with safety lead-in study to assess the safety and efficacy of DPX-Survivac, low dose cyclophosphamide, and pembrolizumab combination therapy in subjects with selected advanced and recurrent solid tumours. Two ovarian cancer arms will be recruited and randomized in this study, one with and one without cyclophosphamide. All other cohorts will be single arm, receiving treatment with the triple combination.

Up to 20 subjects, from any cohort, will be enrolled to assess the safety of study treatments before the study moves to the expansion phase. Once the safety lead-in is completed, the five cohorts will be expanded to recruit additional subjects following a Simon two stage design. Enrollment in the ovarian cancer cohort will be randomized 1:1 into two arms.

• Study Type: Interventional
• Enrollment (Anticipated): 184
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6R3J7
      • William Osler Health System
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Center
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Southlake Regional Health Center
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Research Institute
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre hospitalier de l'Université de Montréal (CHUM)
    • Québec, Quebec, Canada, G1R 2J6
      • CHU de Quebec-Universite Laval
• United States
  • Arizona
    • Tucson, Arizona, United States, 58724
      • The University of Arizona Cancer Center
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center: Samuel Oschin Comprehensive Cancer Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital, Lynn Cancer Institute
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates of the Treasure Coast
    • Saint Petersburg, Florida, United States, 33709
      • Comprehensive Hematology and Oncology
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute: The Emory Clinic
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Brown Graham Cancer Center:University of Louisville Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health, Virginia Piper Cancer Institute
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Christus St. Vincent Regional Cancer Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital
  • Ohio
    • Toledo, Ohio, United States, 43614
      • University of Toledo
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center
    • Houston, Texas, United States, 77030
      • MD Anderson

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Subjects with advanced or metastatic solid tumours who have completed treatment with first line therapy:

  1. Epithelial ovarian, fallopian tube, or peritoneal cancer
  2. Hepatocellular carcinoma
  3. Non-small cell lung cancer
  4. Urothelial cancer
  5. Microsatellite instability high solid tumours, other than the above indications
• Radiologic and/or biochemical evidence of disease progression
• Completion of pre-treatment tumour biopsy
• Must have measurable disease by RECIST v1.1
• Ambulatory with an ECOG 0-1
• Life expectancy ≥ 6 months
• Meet protocol-specified laboratory requirements

Key Exclusion Criteria:

• Chemotherapy or immunotherapy within treatment within 28 days of start of study treatment
• Radiotherapy within treatment within 2 weeks of start of study treatment
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor where subject was discontinued from that treatment due to a Grade 3 or higher immune-related toxicity
• For NSCLC subjects: Known EGFR mutations or ALK rearrangements
• Prior receipt of survivin-based vaccine(s) and/or immunotherapies
• Concurrent second malignancy other than non-melanoma skin cancer, cervical carcinoma in situ, or controlled bladder cancer
• Clinical ascites or pleural fluid that cannot be managed
• Malignant bowel obstruction or recent history of bowel obstruction
• For OvCa, subjects with any single lesion greater than 5 cm
• Autoimmune disease requiring treatment within the last two years (except replacement therapy)
• Recent history of thyroiditis
• Any history of (non-infectious) pneumonitis that required steroid therapy or current pneumonitis
• Presence of a serious acute or chronic infection
• Active CNS metastases and/or carcinomatous meningitis
• GI condition that might limit absorption of oral agents
• Allogenic tissue/solid organ transplant
• 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 live attenuated vaccines
• Acute or chronic skin and/or microvascular disorders
• Edema or lymphedema in the lower limbs > grade 2
• Severe hypersensitivity (≥ Grade 3) to pembrolizumab

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 (All cohorts); DPX-Survivac, Cyclophosphamide, Pembrolizumab	Other: DPX-Survivac; SubQ injection (q9w); Drug: Cyclophosphamide; PO (BID); Drug: Pembrolizumab; IV Infusion (q3w); Other Names: MK-3475
Experimental: Arm 2 (Ovarian cohort only); DPX-Survivac, Pembrolizumab	Other: DPX-Survivac; SubQ injection (q9w); Drug: Pembrolizumab; IV Infusion (q3w); Other Names: MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy as measured by objective response rate	Centrally evaluated using RECIST v1.1	Approximately 24 months
Safety as measured by the rate of adverse events	Using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Centrally evaluated using iRECIST	Approximately 24 months
Duration of response		Approximately 24 months
Disease control rate		Approximately 24 months
Progression Free Survival		Approximately 24 months
Overall survival		Approximately 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cell mediated immunology	As measured by antigen specific immune response in peripheral blood	Approximately 24 months
Changes in immune cell infiltration	As measured by multiplex immunohistochemistry	Approximately 24 months

Collaborators and Investigators

• Sponsor: ImmunoVaccine Technologies, Inc. (IMV Inc.)
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: February 7, 2019
• First Submitted That Met QC Criteria: February 7, 2019
• First Posted (Actual): February 11, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Immunotherapy; Anti-PD-1; Bladder; MK-3475; Ovarian; T cell activation; Non-small Cell Lung; Microsatellite Instability-High; Survivin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Genomic Instability; Carcinoma, Hepatocellular; Microsatellite Instability; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Pembrolizumab
• Other Study ID Numbers: P1719-SUR-Z11; Keynote 903 (Other Identifier: Sponsor)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No