Maveropepimut-S (MVP-S) and Low-Dose CPA in Patients With Platinum-Resistant Ovarian Cancer

Study Overview
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Brief Summary
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Phase 2, single arm, study to assess the efficacy and safety of maveropepimut-S (MVP-S) and low-dose cyclophosphamide (CPA) in subjects with recurrent, platinum resistant ovarian cancer.

Detailed Description
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A Simon two-stage statistical design to assess MVP-S in combination with low dose CPA in platinum-resistant epithelial ovarian cancer patients who have received no greater than 4 previous lines of anti-cancer therapy. MVP-S, previously called DPX-Survivac, was recently evaluated in a small Phase 2 single arm study of ovarian cancer patients known as DeCidE1 (NCT02785250).

Official Title
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Phase 2b Single Arm Study of Maveropepimut-S and Low-Dose Cyclophosphamide in Subjects With Platinum-Resistant, Epithelial Ovarian Cancer.

Conditions
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Platinum-resistant Epithelial Ovarian Cancer

Intervention / Treatment
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* Other: Maveropepimut-S
* Drug: Cyclophosphamide 50mg


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer, histologically diagnosed high-grade serous Platinum-resistant disease (relapsing within 3-6 months after completion of initial platinum-based treatment). Patients progressing at any time on or after ≥ 2nd platinum-based therapy are eligible. Received ≤ 4 prior lines of anti-cancer therapy for ovarian cancer, including at least one platinum-based therapy Evidence of progressive disease Measurable disease (RECIST v1.1) with at least one non-target lesion accessible by image-guided biopsy. No single lesion may be larger than 4 cm in diameter. Completed pre-treatment tumor biopsy and willing to undergo on-treatment tumor biopsy ECOG 0-1 Live expectancy ≥ 6 months Meet protocol-specified laboratory requirements Key Exclusion Criteria: Concurrent chemotherapy drugs, anti-cancer therapy or anti-neoplastic hormonal therapy, or radiotherapy Prior receipt of survivin-based vaccines/therapy, immune checkpoint inhibitors, IDO inhibitor, or cell-based therapy Non-epithelial tumor origin of the ovary, fallopian tube, or peritoneum Clinical ascites Concurrent second malignancy other than basal or squamous cell skin cancer, cervical carcinoma in situ, or Stage I or II caner in complete remission GI condition that might limit absorption of oral agents Recent history of thyroiditis History of autoimmune disease requiring treatment within the last two years (except paraneoplastic syndrome, vitiligo, or diabetes) History of bowel obstruction related to the disease Presence of a serious acute infection or chronic infection Uncontrolled concurrent illness or history of significant cardiac or pulmonary disfunction Myocardial infarction or cerebrovascular event within past 6 months Known central nervous system (CNS) or leptomeningeal metastasis (brain metastases) Clinically significant illness or major surgery within past 28 days or anticipated need for major surgery during study treatment Ongoing treatment with steroid therapy or other immunosuppressive Receipt of live attenuated vaccines Edema or lymphedema in the lower limbs > grade 2 Acute or chronic skin and/or microvascular disorders

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MVP-S + CPA<br>All subjects will receive two doses of maveropepimut-S (q3w) followed by up to six doses (q8w) plus low-dose cyclophosphamide on a repeating cycle of one week on/one week off. | Other: Maveropepimut-S<br>* SC injection on days 7, 28, then q8w<br>* Other names: DPX-Survivac;Drug: Cyclophosphamide 50mg<br>* PO BID, one week on, one week off<br>* Other names: Cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | per RECIST v1.1 criteria | up to 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | per iRECIST criteria | up to 13 months | 
| Duration of Response (DOR) |  | up to 23 months | 
| Disease Control Rate (DCR) |  | up to 13 months | 
| Time to Progression (TTP) |  | up to 23 months | 
| Progression Free Survival (PFS) |  | up to 23 months | 
| Progression Free Survival (6m PFS) |  | at 6 months | 
| Overall Survival (OS) |  | up to 23 months | 
| CA-125 Response | monthly measurements | up to 13 months | 
| Frequency of adverse events | graded using NCI CTCAE v5.0 | up to 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T cell education, DPX-Survivac, Immunotherapy, Platinum-resistant (PROC), High grade serous (HGSOC)