Advaxis, Inc., a clinical-stage biotechnology company developing cancer immunotherapies, announced that the US Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to conduct a phase 1/2 clinical study to evaluate the combination of ADXS-PSA (ADXS31-142) with Keytruda (pembrolizumab), marketed by Merck & Co., Inc., in patients with previously treated, metastatic castration-resistant prostate cancer (mCRPC). The clinical trial, which will be the first-in-human study of Advaxis’s lead Lm-LLO immunotherapy product candidate in prostate cancer, is expected to begin patient enrollment in the first quarter of 2015.

The open-label phase 1/2 clinical trial is designed to evaluate the safety and efficacy of ADXSPSA as a monotherapy and in combination with Keytruda, the first anti-PD-1 (programmed death receptor-1) therapy approved in the United States. Keytruda is developed and marketed by Merck.

The phase 1 part of the study will be a dose-escalating study designed to establish the maximum tolerated dose of ADXS-PSA when used alone and in combination with Keytruda. The phase 2 portion will assess the safety and efficacy of the combination immunotherapy regimen.

Advaxis and Merck will collaboratively oversee the conduct of the study and will use the results from the trial to determine the future clinical development program for the combination.

“Combinations of immunotherapies are the future of cancer research,” stated Daniel J.O’Connor, president and chief executive officer of Advaxis. “We are extremely pleased with FDA’s acceptance of this IND because it gives us the opportunity to conduct clinical trials ofADXS-PSA in combination with an important, FDA approved PD-1 inhibitor, Keytruda.”

O’Connor continued, “This open-label study will provide Advaxis clinical data by which we can evaluate the potential of our proprietary Lm-LLO immunotherapy technology to enhance the activity of an anti-PD-1 antibody. During preclinical studies, our immunotherapies demonstrated a synergistic anti-tumor immune response when combined with a PD-1 inhibitor. We look forward to the possibility of seeing these encouraging results again, this time in a clinical setting, with the hopes of offering a promising alternative treatment option for patients diagnosed with an aggressive and difficult to treat form of prostate cancer.”

ADXS-PSA and Keytruda are members of a new class of cancer treatments known as immunotherapies, which are designed to enhance the body’s own defenses in fighting cancer.

Data from preclinical studies suggest that Advaxis Lm-LLO immunotherapies in combination with a PD-1 inhibitor may lead to an enhanced anti-tumor immune response.

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.

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.