Date: 2015-04-08
Type of information: Initiation of patient enrollment
phase: 1-2
Announcement: initiation of patient enrollment
Company: Advaxis (USA - NJ) Merck&Co (USA - NJ)
Product: ADXS-PSA/ADXS31-142 and Keytruda® (pembrolizumab)
Action
mechanism: cell immunotherapy/monoclonal antibody/immune checkpoint inhibitor. ADXS-PSA is an Lm-LLO (listeriolysin O) 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. Keytruda®(pembrolizumab) 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.
Disease: metastatic castration-resistant prostate cancer (mCRPC)
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: KEYNOTE-046 is a multicenter, dose determining, open-label Phase 1/2 study designed to evaluate the safety and efficacy of ADXS-PSA as a monotherapy and in combination with Keytruda® in approximately 51 mCRPC patients. Part A of the study will be a dose escalating study designed to establish the maximum tolerated dose of ADXS-PSA as a monotherapy. Part B will consist of a dose escalating trial of ADXS-PSA in combination with Keytruda®, followed by an expansion cohort phase. The primary objective is to evaluate safety and tolerability of the two immunotherapies, with the secondary objective to evaluate anti-tumor activity and progression-free survival (PFS). (NCT02325557)
Latest
news: * On April 8, 2015, Advaxis, a clinical-stage biotechnology company developing cancer immunotherapies, and Merck&Co announced that enrollment has initiated in the Phase 1/2 clinical trial evaluating the combination of ADXS-PSA (ADXS31-142), an investigational Lm-LLO immunotherapy, and Keytruda® (pembrolizumab), the first 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, KEYNOTE-046, is the 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® in the treatment of advanced prostate cancer. 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 KEYNOTE-046 will determine the future clinical development program for the combination.
