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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

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

Intervention / Treatment
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* Other: DPX-Survivac
* Drug: Cyclophosphamide
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects with advanced or metastatic solid tumours who have completed treatment with first line therapy: Epithelial ovarian, fallopian tube, or peritoneal cancer Hepatocellular carcinoma Non-small cell lung cancer Urothelial cancer 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 (All cohorts)<br>DPX-Survivac, Cyclophosphamide, Pembrolizumab | Other: DPX-Survivac<br>* SubQ injection (q9w)<br>Drug: Cyclophosphamide<br>* PO (BID)<br>Drug: Pembrolizumab<br>* IV Infusion (q3w)<br>* Other names: MK-3475;|
| Experimental: Arm 2 (Ovarian cohort only)<br>DPX-Survivac, Pembrolizumab | Other: DPX-Survivac<br>* SubQ injection (q9w)<br>Drug: Pembrolizumab<br>* IV Infusion (q3w)<br>* Other names: MK-3475;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T cell activation, Immunotherapy, Ovarian, Hepatocellular Carcinoma, Non-small Cell Lung, Bladder, Microsatellite Instability-High, Survivin, Anti-PD-1, MK-3475