ADXS31142 Immunotherapy ± Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: Open-Label Phase I/II KEYNOTE-046 Study

Mark N Stein; Lawrence Fong; Ronald Tutrone; Anthony Mega; Elaine T Lam; Megan Parsi; Surya Vangala; Andres A Gutierrez; Naomi B Haas

doi:10.1093/oncolo/oyac048

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.

Authors

Mark N Stein¹, Lawrence Fong², Ronald Tutrone³, Anthony Mega⁴, Elaine T Lam⁵, Megan Parsi⁶, Surya Vangala⁶, Andres A Gutierrez⁶, Naomi B Haas⁷

Affiliations

¹ Columbia University Medical Center, New York, NY, USA.
² University of California, San Francisco, CA, USA.
³ Chesapeake Urology Research Associates, Towson, MD, USA.
⁴ Lifespan Oncology Clinical Research, Rhode Island Hospital, Providence, RI, USA.
⁵ University of Colorado Cancer Center, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
⁶ Advaxis, Monmouth Junction, NJ, USA.
⁷ Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

Background: ADXS31-142 is an attenuated Listeria monocytogenes-based immunotherapy targeting prostate-specific antigen (PSA), being evaluated as monotherapy and combined with pembrolizumab for metastatic castration-resistant prostate cancer (mCRPC).

Patients and methods: The 2-part phase I/II KEYNOTE-046 study enrolled men with mCRPC who have progressed after 2 or fewer prior systemic treatment regimens in the metastatic setting. In Part A, intravenous ADXS31-142 monotherapy was given every 3 weeks (q3w) to 3 dose-escalation cohorts. In Part B, ADXS31-142 (1 × 109 colony-forming units) plus pembrolizumab (200 mg) was administered intravenously q3w for 3 doses with a fourth pembrolizumab dose 3 weeks later (12-week cycles) for up to 24 months or until progression/toxicity. Endpoints included safety, overall response rate, progression-free survival (PFS), overall survival (OS), and immunogenicity.

Results: Fifty patients received ADXS31-142 alone (n = 13) or with pembrolizumab (n = 37). Among the 37 RECIST-evaluable patients (n = 8 Part A; n = 29 Part B), there were no objective responses. Median PFS was 2.2 months (95% CI: 0.8-7.4) with monotherapy and 5.4 months (95% CI: 2.3-7.9) with the combination; median OS was 7.8 months (95% CI: 4.4-18.5) and 33.7 months (95% CI: 15.4-not evaluable), respectively. Promising OS benefit was observed in combination-treated patients who had received prior docetaxel (16.0 months, 95% CI: 6.4-34.6; n = 20) and those with visceral metastasis (16.4 months, 95% CI 4.0-not evaluable; n = 11). All patients had ≥1 treatment-related adverse event, mostly grade 1/2 manageable events. No additive toxicity was observed with combination treatment.

Conclusions: Combining ADXS31-142 with pembrolizumab was safe and well tolerated. The observed OS in mCRPC warrants further testing of this combination.

Clinical trial registration: NCT02325557.

Keywords: Lm vectors; immunotherapy; metastatic castration-resistant prostate cancer (mCRPC); pembrolizumab; prostate-specific antigen (PSA).

Publication types

Clinical Trial, Phase I
Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized / pharmacology
Antibodies, Monoclonal, Humanized / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Docetaxel / therapeutic use
Humans
Immunotherapy
Male
Prostatic Neoplasms, Castration-Resistant* / drug therapy
Prostatic Neoplasms, Castration-Resistant* / pathology

Substances

Antibodies, Monoclonal, Humanized
Docetaxel
pembrolizumab

Associated data

ClinicalTrials.gov/NCT02325557