Clinical trial NCT03836352: Study of an Immunotherapeutic, DPX-Survivac, in Combination With Low Dose Cyclophosphamide & Pembrolizumab, in Subjects With Selected Advanced & Recurrent Solid Tumors
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Ovarian Cancer
Hepatocellular Carcinoma
Non-small Cell Lung Cancer
Bladder Cancer
Microsatellite Instability-High
Keywords: T cell activation
Immunotherapy
Ovarian
Hepatocellular Carcinoma
Non-small Cell Lung
Bladder
Microsatellite Instability-High
Survivin
Anti-PD-1
MK-3475
Lead sponsor: ImmunoVaccine Technologies, Inc. (IMV Inc.)
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-02-11
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy as measured by objective response rate
timeFrame: Approximately 24 months
measure: Safety as measured by the rate of adverse events
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Objective response rate
timeFrame: Approximately 24 months
measure: Duration of response
timeFrame: Approximately 24 months
measure: Disease control rate
timeFrame: Approximately 24 months
measure: Progression Free Survival
timeFrame: Approximately 24 months
measure: Overall survival
timeFrame: Approximately 24 months
Other outcomes:
measure: Cell mediated immunology
timeFrame: Approximately 24 months
measure: Changes in immune cell infiltration
timeFrame: Approximately 24 months
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center: Samuel Oschin Comprehensive Cancer Center
state: California
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital, Lynn Cancer Institute
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Saint Petersburg
country: United States
facility: Comprehensive Hematology and Oncology
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute: The Emory Clinic
state: Georgia
city: Louisville
country: United States
facility: James Brown Graham Cancer Center:University of Louisville Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Cancer Institute
state: Louisiana
city: Minneapolis
country: United States
facility: Allina Health, Virginia Piper Cancer Institute
state: Minnesota
city: Santa Fe
country: United States
facility: Christus St. Vincent Regional Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Mineola
country: United States
facility: NYU Winthrop Hospital
state: New York
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Brampton
country: Canada
facility: William Osler Health System
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Center
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Center
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Québec
country: Canada
facility: CHU de Québec-Université Laval
state: Quebec
Study officials:
References: