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

Ovarian Cancer Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03836352
• Other study ID #: P1719-SUR-Z11
• Secondary ID: Keynote 903
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 21, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2022
• Source: ImmunoVaccine Technologies, Inc. (IMV Inc.)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 184
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Microsatellite Instability
• Microsatellite Instability-High
• Non-small Cell Lung Cancer
• Ovarian Cancer

Intervention

Other:
• DPX-Survivac
SubQ injection (q9w)

Drug:
• Cyclophosphamide
PO (BID)
• Pembrolizumab
IV Infusion (q3w)

Locations

Country	Name	City	State
Canada	William Osler Health System	Brampton	Ontario
Canada	Juravinski Cancer Center	Hamilton	Ontario
Canada	Centre hospitalier de l'Université de Montréal (CHUM)	Montreal	Quebec
Canada	McGill University Health Center	Montreal	Quebec
Canada	Southlake Regional Health Center	Newmarket	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	CHU de Québec-Université Laval	Québec	Quebec
Canada	Sunnybrook Research Institute	Toronto	Ontario
United States	Winship Cancer Institute: The Emory Clinic	Atlanta	Georgia
United States	Boca Raton Regional Hospital, Lynn Cancer Institute	Boca Raton	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	MD Anderson	Houston	Texas
United States	Cedars Sinai Medical Center: Samuel Oschin Comprehensive Cancer Center	Los Angeles	California
United States	James Brown Graham Cancer Center:University of Louisville Hospital	Louisville	Kentucky
United States	NYU Winthrop Hospital	Mineola	New York
United States	Allina Health, Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Ochsner Cancer Institute	New Orleans	Louisiana
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Comprehensive Hematology and Oncology	Saint Petersburg	Florida
United States	Christus St. Vincent Regional Cancer Center	Santa Fe	New Mexico
United States	University of Toledo	Toledo	Ohio
United States	The University of Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
ImmunoVaccine Technologies, Inc. (IMV Inc.)	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cell mediated immunology	As measured by antigen specific immune response in peripheral blood	Approximately 24 months
Other	Changes in immune cell infiltration	As measured by multiplex immunohistochemistry	Approximately 24 months
Primary	Efficacy as measured by objective response rate	Centrally evaluated using RECIST v1.1	Approximately 24 months
Primary	Safety as measured by the rate of adverse events	Using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Approximately 24 months
Secondary	Objective response rate	Centrally evaluated using iRECIST	Approximately 24 months
Secondary	Duration of response		Approximately 24 months
Secondary	Disease control rate		Approximately 24 months
Secondary	Progression Free Survival		Approximately 24 months
Secondary	Overall survival		Approximately 24 months