ADXS31-142 Immunotherapy ± Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: 
Open-Label Phase I/II KEYNOTE-046 Study.

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).

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.

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.

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

NCT02325557.

The oncologist. 2022 Apr 03 [Epub ahead of print]

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

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

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