ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Patients With Prostate Cancer

Study Overview
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Brief Summary
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A Phase 1/2 multicenter, dose determining, open-label study of ADXS31-142 monotherapy and a combination of ADXS31-142 with Pembrolizumab (MK-3475) in patients with metastatic castration-resistant prostate cancer. Part A will be dose-determining of ADXS31-142 monotherapy. Part B will be dose-determining of ADXS31-142 and Pembrolizumad (MK-3475) in combination. Part B expansion will treat additional patients with the recommended dose from Part B.

Detailed Description
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Part A of the study will be an open-label, Phase 1, multicenter, non-randomized, dose-determining trial of ADX31-142 monotherapy in subjects with metastatic castration-resistant prostate cancer (mCRPC). The dose determining phase is intended to select a recommended Phase 2 dose (RP2D) for Part B. Part B of the study will be an open-label, Phase 1-2, multicenter, non-randomized dose-determining trial of ADXS31-142 in combination with pembrolizumab (MK-3475) in subjects with mCRPC. Part B will consist of a dose-determination phase followed by an expansion cohort phase. The dose-determining phase is intended to select a RP2D for the combination. Dose escalation/de-escalation for this study will be explored by applying the mTPI design.

Official Title
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A Phase 1-2 Dose-Escalation and Safety Study of ADXS31-142 Alone and of ADXS31-142 in Combination With Pembrolizumab (MK-3475) in Patients With Previously Treated Metastatic Castration-Resistant Prostate Cancer

Conditions
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Cancer, Prostate Cancer

Intervention / Treatment
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* Drug: ADXS31-142
* Drug: ADXS31-142 + Pembrolizumab (MK-3475)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be willing and able to provide written informed consent for the trial. Be 18 years of age or older on day of signing informed consent. Have progressive metastatic castration resistant prostate cancer, on androgen deprivation therapy, based on as least one of the following criteria: PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval with a minimum PSA of 2 ng/ml. Progression of bi-dimensionally measurable soft tissue (nodal metastasis) assessed within 1 month prior to registration by a CT scan or MRI of the abdomen and pelvis. Progression of bone disease (evaluable disease) (new bone lesion(s)) by bone scan. Has discontinued antiandrogens (bicalutamide, nilutamide) >6 weeks and enzalutamide >4 weeks prior to Day 1 of trial treatment Have a performance status of 0 or 1 on the ECOG Performance Scale. Exclusion Criteria: Received more than 3 prior systemic treatment regimens with chemotherapy , hormonal, or immunotherapy in the metastatic setting or received more than 1 prior chemotherapeutic regimen in the metastatic setting Has a diagnosis of immunodeficiency or is receiving any systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Day 1 of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to a previously administered agent. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in a Merck MK-3475 clinical trial. Has a contraindication to administration of ampicillin or trimethoprim/ sulfamethoxazole. Has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants, and venous access devices (e.g., Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device and/or implant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>Patients will receive ADXS31-142 monotherapy. Dosing will start at 1 x 10^9 cfu IV and escalate to 1 x 10^10 if appropriate. | Drug: ADXS31-142<br>* starting at 1x10^9 cfu IV<br>|
| Experimental: Part B/Expansion<br>Patients will receive ADXS31-142 and pembrolizumab (MK-3475) in combination. Dosing of ADXS31-142 will start at one dose level less that appropriate in Part A in combination with 200 mg of pembrolizumab. Dosing of ADXS31-142 will be escalated if appropriate | Drug: ADXS31-142 + Pembrolizumab (MK-3475)<br>* starting at dose from Part A + 200mg of Pembrolizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events in each dose level | Number of subjects with adverse events in each dose level | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival as measured by RECIST 1.1 or ir RECIST | Progression Free Survival as measured by RECIST 1.1 or ir RECIST | 2 years |