Clinical trial NCT02325557: ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Participants With Previously Treated Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cancer
Prostate Cancer
Lead sponsor: Advaxis, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2014-12-25
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: From first dose up to 30 days after last dose (maximum duration: 108 weeks)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From screening until progression or death (maximum duration: 104 weeks)
measure: Objective Response Rate According to Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
timeFrame: From screening until progression or death (maximum duration: 104 weeks)
measure: Progression-free Survival, Assessed by RECIST Version 1.1
timeFrame: From screening until progression or death (maximum duration: 104 weeks)
measure: Overall Survival
timeFrame: From screening until progression or death (maximum duration: 104 weeks)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Recruiting
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center (UCHSC)
state: Colorado
city: Rockville
country: United States
facility: Recruiting
state: Maryland
city: Towson
country: United States
facility: Recruiting
state: Maryland
city: New Brunswick
country: United States
state: New Jersey
city: Philadelphia
country: United States
facility: Recrutiing
state: Pennsylvania
city: Philadelphia
country: United States
facility: Site
state: Pennsylvania
city: Providence
country: United States
facility: Recruiting
state: Rhode Island
Study officials:
References:
citation: Stein MN, Fong L, Tutrone R, Mega A, Lam ET, Parsi M, Vangala S, Gutierrez AA, Haas NB. ADXS31142 Immunotherapy +/- Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: Open-Label Phase I/II KEYNOTE-046 Study. Oncologist. 2022 Jun 8;27(6):453-461. doi: 10.1093/oncolo/oyac048.