adxs31-142 alone and in combination with pembrolizumab (mk-3475) in participants with previously treated metastatic castration-resistant prostate cancer (mcrpc)

Conditions: Cancer; Prostate Cancer

Summary: a phase 1/2 multicenter, dose determining, open-label study of adxs31-142 monotherapy and a combination of adxs31-142 and pembrolizumab (mk-3475) in participants with metastatic castration-resistant prostate cancer. part a will be dose-determining part of adxs31-142 monotherapy. part b will be dose-determining part of adxs31-142 and pembrolizumab (mk-3475) in combination. part b expansion will treat additional participants with the recommended dose from part b.

part a of the study will be an open-label, phase 1, multicenter, non-randomized, dose-determining trial of adxs31-142 monotherapy in participants with 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 participants 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 an rp2d for the combination. dose escalation/de-escalation for this study will be explored by applying the modified toxicity probability interval design.

Eligibility criteria:
inclusion criteria: 1. have progressive mcrpc, on androgen deprivation therapy, based on at least one of the following criteria: 1. prostate-specific antigen (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. 2. progression of bi-dimensionally measurable soft tissue (nodal metastasis) assessed within 1 month prior to registration by computed tomography (ct) scan or magnetic resonance imaging (mri) of the abdomen and pelvis. 3. progression of bone disease (evaluable disease) (new bone lesion\[s\]) by bone scan. 2. has discontinued antiandrogens (bicalutamide, nilutamide) \>6 weeks and enzalutamide \>4 weeks prior to day 1 of trial treatment 3. have a performance status of 0 or 1 on the eastern cooperative oncology group (ecog) performance scale. exclusion criteria: 1. 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 2. 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. 3. 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. 4. 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. 5. has received prior therapy with an anti-programmed cell death protein-1 (pd-1), anti-programmed death-ligand-1 (pd-l1), or anti-programmed death-ligand-2 (pd-l2) agent or if the participant has previously participated in a merck mk-3475 clinical trial. 6. has a contraindication to administration of ampicillin or trimethoprim/ sulfamethoxazole. 7. 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.