Advaxis, Inc., a clinical-stage biotechnology company developing cancer immunotherapies, has entered into a clinical trial collaboration agreement with Merck, known as MSD outside the United States and Canada, through its subsidiaries, to evaluate the combination of Advaxis’s Lm-LLO cancer immunotherapy, ADXS-PSA, with Merck’s investigational anti PD-1 antibody, pembrolizumab.

The planned clinical trial will evaluate the safety and efficacy of ADXS-PSA as monotherapy and in combination with pembrolizumab in a phase 1/2 study of patients with previously treated metastatic, castration-resistant prostate cancer.

Both ADXS-PSA and pembrolizumab are investigational members of a new class of cancer treatments known as immunotherapies that are designed to enhance the body’s own defenses in fighting cancer. Preclinical evidence suggests that Advaxis Lm-LLO immunotherapies in combination with a PD-1 inhibitor may lead to an enhanced anti-tumour immune response.

“We are excited to be working with Merck. Equally as exciting is the combination potential of our Lm-LLO immunotherapy with Merck’s anti-PD-1 immune checkpoint inhibitor,” commented Daniel J. O’Connor, president and chief executive officer of Advaxis. “We believe the combination of Advaxis Lm-LLO cancer immunotherapies and checkpoint inhibitors holds significant promise for the treatment of prostate and other cancers.”

Under the terms of the agreement, Advaxis and Merck will collaborate to evaluate the ADXS-PSA/pembrolizumab combination as a treatment for prostate cancer. The phase 1 part of the trial is designed to establish a recommended dose regimen for ADXS-PSA alone and combined with pembrolizumab, and the phase 2 portion will assess the safety and efficacy of the combination. Advaxis will sponsor and fund the study and Merck will provide pembrolizumab. The companies will collaboratively oversee the conduct of the study, which is planned to begin in early 2015. Results from the study will be used to determine the path for further clinical development of the combination.

“Collaborations such as this are an integral part of Merck’s strategy to evaluate the potential of pembrolizumab in multiple combinations for a broad range of cancers,” said Dr. Eric Rubin, vice president oncology, Merck Research Laboratories. “We look forward to working with Advaxis to evaluate this novel investigational combination immunotherapy for the treatment of advanced prostate cancer.”

According to the American Cancer Society, prostate cancer is the most common type of cancer found in American men, other than skin cancer. Prostate cancer is the second leading cause of cancer death in men, behind only lung cancer. One man in six will get prostate cancer during his lifetime, and one man in 36 will die of this disease.

ADXS-PSA is an Lm-LLO immunotherapy that is designed to target the PSA antigen 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. The Advaxis approach is also designed to inhibit the Treg and MDSC cells that contribute to immunologic tolerance of prostate cancer. In preclinical analysis, ADXS-PSA inhibits the immunosuppression caused by Treg and MDSC cells localized inside tumours that we believe promotes immunologic tolerance of prostate cancer.

Pembrolizumab (MK-3475) is an investigational, humanized, monoclonal antibody against PD-1 designed to reactivate anti-tumour immunity. Pembrolizumab exerts dual ligand blockade of the PD-1 pathway by inhibiting the interaction of PD-1 on T cells with its ligands PD-L1 and PD-L2.

Pembrolizumab is currently being evaluated across more than 30 types of cancers, as monotherapy and in combination. It is anticipated that by the end of 2014, the pembrolizumab development program will grow to more than 24 clinical trials, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide.

Advaxis is a clinical-stage biotechnology company developing multiple cancer immunotherapies based on its proprietary platform intended to redirect the immune system to kill cancer.