US-based biotechnology firm Advaxis has received clearance from the US Food and Drug Administration (FDA) for its investigational new drug (IND) application to start a Phase I/II clinical trial to evaluate the combination of ADXS-PSA (ADXS31-142) with Merck's Keytruda in patients with previously treated, metastatic castration-resistant prostate cancer (mCRPC).
Patient enrolment in the open-label Phase I/II clinical trial is expected to start in the first quarter of 2015.
According to Advaxis, the trial will be the first-in-human study of its lead Lm-LLO immunotherapy product candidate in prostate cancer.
The trial is designed to evaluate the safety and efficacy of ADXS-PSA as a monotherapy and in combination with Keytruda, the first anti- programmed death receptor-1 (PD-1) therapy approved in the US.
The Phase I part of the trial will be a dose-escalating study designed to establish the maximum tolerated dose of ADXS-PSA when used alone and in combination with Keytruda, while the Phase II portion will evaluate the safety and efficacy of the combination immunotherapy regimen.
The two firms will collaboratively oversee the conduct of the trial and will use the results to determine the future clinical development programme for the combination.
Advaxis president and chief executive officer Daniel O'Connor said: "Combinations of immunotherapies are the future of cancer research.
"We are extremely pleased with FDA's acceptance of this IND because it gives us the opportunity to conduct clinical trials of ADXS-PSA in combination with an important, FDA approved PD-1 inhibitor, Keytruda.
"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-tumour immune response when combined with a PD-1 inhibitor."
Both ADXS-PSA and Keytruda are members of a new class of cancer treatments known as immunotherapies, which are designed to improve the body's own defences in fighting cancer.
The company said that preclinical data suggest that Advaxis Lm-LLO immunotherapies in combination with a PD-1 inhibitor may lead to an improved anti-tumour immune response.
ADXS-PSA is an Lm-LLO immunotherapy designed to target the prostate-specific antigen (PSA), a protein produced exclusively by prostate cells associated with prostate cancer.
Image: Micrograph showing a prostate cancer (conventional adenocarcinoma) with perineural invasion. Photo: courtesy of Nephron