ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Participants With Previously Treated Metastatic Castration-Resistant Prostate Cancer (mCRPC)

NCT ID: NCT02325557

Last Updated: 2024-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-04
• Study Completion Date: 2020-01-22

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.

Conditions

Cancer; Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: ADXS31-142

Participants received ADXS31-142 1 × 10^9 colony-forming units (CFU), 5 × 10^9 CFU, or

1 × 10^10 CFU intravenously (IV) every 3 weeks (Q3W) in a 12-week cycle for up to 24 months or until disease progression or discontinuation.

Group Type: EXPERIMENTAL

ADXS31-142

Intervention Type: DRUG

ADXS31-142 IV infusion

Part B: ADXS31-142 + Pembrolizumab

Participants received ADXS31-142 1 × 10\^9 CFU) IV Q3W (in a 12-week cycle) in combination with 200 mg pembrolizumab IV Q3W for three times, with a fourth pembrolizumab dose 3 weeks later (in 12 week-cycles) for up to 24 months or until disease progression or discontinuation.

Group Type: EXPERIMENTAL

ADXS31-142

Intervention Type: DRUG

ADXS31-142 IV infusion

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab IV infusion

Interventions

ADXS31-142

ADXS31-142 IV infusion

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab IV infusion

Intervention Type: DRUG

Other Intervention Names

MK-3475

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Advaxis, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Recruiting

San Francisco, California, United States

University of Colorado Health Sciences Center (UCHSC)

Aurora, Colorado, United States

Recruiting

Rockville, Maryland, United States

Recruiting

Towson, Maryland, United States

New Brunswick, New Jersey, United States

Recrutiing

Philadelphia, Pennsylvania, United States

Site

Philadelphia, Pennsylvania, United States

Recruiting

Providence, Rhode Island, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 35373299 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177110/

Related Info

Other Identifiers

KEYNOTE-046

Identifier Type: OTHER

Identifier Source: secondary_id

ADXS142-03

Identifier Type: -

Identifier Source: org_study_id