On April 1, 2019 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported updated data from the Phase 1/2 KEYNOTE-046 study in metastatic, castration-resistant prostate cancer (mCRPC) (Press release, Advaxis, APR 1, 2019, View Source [SID1234534844]). This trial is being conducted in conjunction with Merck (known as MSD outside the U.S. and Canada) and is evaluating ADXS-PSA, one of Advaxis’ Listeria monocytogenes (Lm)-based immunotherapies, alone and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy.

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Findings will be highlighted in a poster discussion entitled "Effects of ADXS-PSA with or without Pembrolizumab on Survival and Antigen Spreading in Metastatic, Castration-Resistant Prostate Cancer Patients" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting underway in Atlanta. The poster discussion will be held today from 1:00-5:00 p.m. ET and will be led by lead author Mark N. Stein M.D., FACS, Associate Professor of Medical Oncology at Columbia University Medical Center.

KEYNOTE-046 is an open-label, multicenter, dose-determining safety and tolerability Phase 1/2 trial of 50 heavily pretreated patients conducted in two parts (Part A and Part B), with a Phase 2 expansion cohort. The objective of the study is to evaluate ADXS-PSA alone (Part A) and in combination with KEYTRUDA (Part B) for primary endpoints that include safety, tolerability and dosing. Secondary endpoints include anti-tumor activity and progression-free survival, and exploratory endpoints include associations between biomarkers of immunologic response (serum PSA) with clinical outcomes.

"There is a pressing need to improve the care and treatment of patients with metastatic, castration-resistant prostate cancer," said Dr. Stein. "Data from 37 patients in the combination arm of KEYNOTE-046 are promising as a median overall survival of 21.1 months was observed. These results compare favorably to standard-of-care therapy and to study results from similar unselected patient populations with bone-predominant disease, which indicates that this combination warrants further investigation."

Key findings from the combination arm of KEYNOTE-046 include the following:

The majority of treatment-related adverse events consisted of transient and reversible Grade 1-2 chills/rigors, fever, hypotension, nausea and fatigue. The combination of ADXS-PSA and pembrolizumab has been well-tolerated, to date, with no additive toxicity observed.
Median overall survival was 21.1 months at data cutoff (February 1, 2019) (95% CI, range 16.0 months to not-yet-reached) in this dataset of 37 patients.
Correlative immune analyses showed T-cell responses against PSA in 75% of subjects and antigen spreading in 85% of subjects.
Broader immune stimulation, including B-cell activation, was observed in the combination arm (n=37) than in the ADXS-PSA monotherapy arm (n=13).
"We are very excited to report the updated ADXS-PSA data today at the AACR (Free AACR Whitepaper) meeting," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "These data show the clinical potential of ADXS-PSA both alone and in combination with KEYTRUDA. It is meaningful that the combination has been well-tolerated in the study population because dose-related toxicities can present challenges for cancer patients, and an additive therapy with a favorable safety and tolerability profile may offer an attractive option for clinicians if developed further in this indication." He concluded, "Based on the prolonged survival data and strong safety profile to date, we believe that continued clinical development of ADXS-PSA in combination with KEYTRUDA is warranted and represents a potentially significant opportunity for Advaxis."

The full abstract is available at www.advaxis.com and the poster will be available on the Company’s website today at 1:00 p.m. ET.

About KEYNOTE-046

KEYNOTE-046 (NCT02325557) is a Phase 1/2 open-label, multicenter, dose-determination and expansion trial that evaluates the safety, tolerability and preliminary clinical activity of ADXS-PSA as monotherapy (Part A; n=14 [13 treated]), and in combination with KEYTRUDA (Part B; n=37) in heavily pretreated patients with progressive and refractory mCRPC.

About ADXS-PSA

ADXS-PSA, one of Advaxis’ Lm-based immunotherapies, utilizes live, attenuated, bioengineered Lm as a vector to deliver PSA directly to antigen presenting cells. Development is being pursued in a clinical trial collaboration and supply agreement with Merck