Merck & Co. Inc. and Advaxis, a clinical-stage biotechnology company developing multiple cancer immunotherapies, have initiated a Phase I/II clinical trial evaluating the combination of ADXS-PSA (ADXS31-142), an investigational Lm-LLO immunotherap by Advaxis, and Merck’s Keytruda (pembrolizumab), an anti-PD-1 (programmed death receptor-1) therapy approved in the United States, in patients with previously treated, metastatic castration-resistant prostate cancer (mCRPC). The clinical trial is a first-in-human study of Advaxis's lead Lm-LLO immunotherapy candidate for prostate cancer. It is the second study initiated to evaluate the use of Keytruda for treating advanced prostate cancer.

ADXS-PSA and Keytruda are members of a class of cancer treatments known as immuno-oncology therapies. Data from preclinical studies suggest that Advaxis Lm-LLO immunotherapies in combination with a PD-1 antibody may lead to an enhanced anti-tumor immune response. The results from the companies’ clinical trial will determine the future clinical development program for the combination.

Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, Keytruda releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. The drug is indicated in the US for treating unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Merck is advancing a broad clinical development program for Keytruda with more than 70 clinical trials ,across more than 30 tumor types and over 8,000 patients, both as a monotherapy and in combination with other therapies

ADXS-PSA is an Lm-LLO immunotherapy that is designed to target the prostate-specific antigen (PSA), a protein produced exclusively by prostate cells that is associated with prostate cancer. The Lm-LLO technology uses bioengineered live attenuated Listeria monocytogenes bacteria. ADXS-PSA secretes the PSA antigen, fused to the powerful immunostimulant tLLO, directly inside the antigen presenting cells that are capable of driving a cellular immune response to PSA-expressing cells. This approach is also designed to inhibit the Treg and myeloid-derived suppressor cells (MDSCs) that contribute to immunologic tolerance of prostate cancer. In preclinical analysis, ADXS-PSA inhibits the immunosuppression caused by Treg and MDSC cells localized inside tumors that may promote immunologic tolerance of prostate cancer.

Source: Merck & Co. Inc.