11 October 2019 - - US-based biotechnology company Advaxis, Inc. (NASDAQ: ADXS) has released updated median overall survival data from its Phase 1/2 KEYNOTE-046 study in metastatic, castration-resistant prostate cancer (mCRPC), the company said.

This trial is being conducted in conjunction with US-based Merck (NYSE: MRK) 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.

At the final data cutoff of September 16, 2019, median overall survival for 37 patients in the combination arm was 33.6 months (95% CI, range 15.4-33.6 months).

This updated median overall survival is an increase from the previous data presented at the American Association for Cancer Research annual meeting in April, where median overall survival was 21.1 months in the combination arm.

These new data, along with additional details from this final predetermined look at the trial results, will be presented at an upcoming medical conference.

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, progression-free survival and overall survival, and exploratory endpoints that include associations between biomarkers of immunologic response (serum PSA) with clinical outcomes.

Enrollment in the study has been completed. 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 Keytruda has appeared to be well-tolerated, to date, with no additive toxicity observed.

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.

Advaxis, Inc. is a clinical-stage biotechnology company focused on the discovery, development and commercialisation of proprietary Lm-based antigen delivery products.

These immunotherapies are based on a platform technology that utilizes live attenuated Listeria monocytogenes bioengineered to secrete antigen/adjuvant fusion proteins.

These Lm-based strains are believed to be a significant advancement in immunotherapy as they integrate multiple functions into a single immunotherapy and are designed to access and direct antigen presenting cells to stimulate anti-tumor T cell immunity, activate the immune system with the equivalent of multiple adjuvants, and simultaneously reduce tumor protection in the tumor microenvironment to enable T cells to eliminate tumors.

Advaxis has three programmes in various stages of clinical development: ADXS-NEO, a personalized neoantigen-directed therapy designed, in principle, for any solid tumor; ADXS-503 for non-small cell lung cancer, from its ADXS-HOT off-the-shelf neoantigen-directed program and ADXS-PSA for prostate cancer.