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

NCT02325557 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: ADXS142-03KEYNOTE-046
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

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.

Conditions

Cancer; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events

  An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Adverse events with onset dates on or after the first dose of study medication and within 30 days following the last dose of study medication were considered "treatment emergent".

  From first dose up to 30 days after last dose (maximum duration: 108 weeks)

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  From screening until progression or death (maximum duration: 104 weeks)

• Objective Response Rate According to Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

  From screening until progression or death (maximum duration: 104 weeks)

• Progression-free Survival, Assessed by RECIST Version 1.1

  From screening until progression or death (maximum duration: 104 weeks)

• Overall Survival

  From screening until progression or death (maximum duration: 104 weeks)

Study Arms (2)

Part A: ADXS31-142

EXPERIMENTAL

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.

Drug: ADXS31-142

Part B: ADXS31-142 + Pembrolizumab

EXPERIMENTAL

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.

Drug: ADXS31-142; Drug: Pembrolizumab

Interventions

ADXS31-142 DRUG

ADXS31-142 IV infusion

Part A: ADXS31-142; Part B: ADXS31-142 + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab IV infusion

Also known as: MK-3475

Part B: ADXS31-142 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have progressive mCRPC, on androgen deprivation therapy, based on at least one of the following criteria:
• 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.
• 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.
• 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 Eastern Cooperative Oncology Group (ECOG) performance scale.

You may not qualify if:

• 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-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.
• 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.

Sponsors & Collaborators

• Advaxis, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

Recruiting

San Francisco, California, United States

Location

University of Colorado Health Sciences Center (UCHSC)

Aurora, Colorado, United States

Location

Recruiting

Rockville, Maryland, United States

Location

Recruiting

Towson, Maryland, United States

Location

Unknown Facility

New Brunswick, New Jersey, United States

Location

Recrutiing

Philadelphia, Pennsylvania, United States

Location

Site

Philadelphia, Pennsylvania, United States

Location

Recruiting

Providence, Rhode Island, United States

Location

Related Publications (1)

• 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.

  PMID: 35373299 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms; Prostatic Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Sumitra Sheeri
• Organization: Advaxis, Inc.

sheeri@advaxis.com

609-423-2528

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2014
• First Posted: December 25, 2014
• Study Start: June 4, 2015
• Primary Completion: August 30, 2019
• Study Completion: January 22, 2020
• Last Updated: April 2, 2024
• Results First Posted: February 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)