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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Prostate Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: ADXS31-142

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States
      • Recruiting
  • Colorado
    • Aurora, Colorado, United States
      • University of Colorado Health Sciences Center (UCHSC)
  • Maryland
    • Rockville, Maryland, United States
      • Recruiting
    • Towson, Maryland, United States
      • Recruiting
  • New Jersey
    • New Brunswick, New Jersey, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Recrutiing
    • Philadelphia, Pennsylvania, United States
      • Site
  • Rhode Island
    • Providence, Rhode Island, United States
      • Recruiting

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: ADXS31-142; ADXS31-142 IV infusion
Experimental: 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.	Drug: Pembrolizumab; Pembrolizumab IV infusion; Other Names: MK-3475; Drug: ADXS31-142; ADXS31-142 IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 was defined as the number of participants with objective evidence of radiologic complete response (CR: disappearance of all target lesions) and partial response (PR: at least a 30% decrease in the sum of the longest diameters of target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions) as determined from investigator response assessments. Disease Control Rates are based upon confirmed events only.	From screening until progression or death (maximum duration: 104 weeks)
Objective Response Rate According to Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)	The ORR according to irRECIST was defined as the number of participants with objective evidence of radiologic immune-related CR (irCR: Disappearance of all target lesions) and immune-related PR (irPR: At least 30% decrease in tumor burden compared with baseline) as determined from investigator response assessments.	From screening until progression or death (maximum duration: 104 weeks)
Progression-free Survival, Assessed by RECIST Version 1.1	Progression-free survival (PFS) was defined as the time from randomization until objective tumor progression based on response evaluation criteria in solid tumors (RECIST) version 1.1 or death. The progressive disease is defined at least a 20% increase in the sum of the longest diameter of target lesions. Participants who had not experienced disease progression or who were still alive at the time of evaluation were censored for the analysis. The PFS was estimated using Kaplan-Meier method.	From screening until progression or death (maximum duration: 104 weeks)
Overall Survival	Overall survival is defined as the time from the date of start of study treatment until death due to any cause. Any participant not died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The OS was estimated using Kaplan-Meier method.	From screening until progression or death (maximum duration: 104 weeks)

Collaborators and Investigators

• Sponsor: Advaxis, Inc.
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2015
• Primary Completion (Actual): August 30, 2019
• Study Completion (Actual): January 22, 2020

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: December 22, 2014
• First Posted (Estimated): December 25, 2014

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: ADXS142-03; KEYNOTE-046 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No