Off-the-Shelf Immunotherapy ADXS-504 Under Evaluation in Biochemically Recurrent Prostate Cancer

Pipeline Report | <b>Pipeline Report: April 2021</b>

Columbia University Irving Medical Center will partner with Advaxis, Inc. to fund a phase 1 clinical trial that seeks to examine the novel off-the-shelf neoantigen immunotherapy agent ADXS-504 in patients with biochemically recurrent prostate cancer.

Columbia University Irving Medical Center will partner with Advaxis, Inc. to fund a phase 1 clinical trial that seeks to examine the novel off-the-shelf neoantigen immunotherapy agent ADXS-504 in patients with biochemically recurrent prostate cancer.1

This phase 1, open-label trial will examine the safety and tolerability of single-agent ADXS-504, administered intravenously in 9 to 18 patients with biochemically recurrent prostate cancer. Patients who are currently receiving androgen ablation therapy will not be eligible for inclusion. Additionally, investigators will assess preliminary clinical and immune responses to the agent.

“Currently, men with biochemically recurrent prostate cancer are either monitored for a period of time without intervention or may be started on medicine to decrease the level of testosterone in the body, which can have significant adverse effects,” Mark Stein, MD, principal investigator of the study and an associate professor of medicine in the Division of Hematology/Oncology at Columbia University Vagelos College of Physicians and Surgeons, stated in a press release. “Therefore, we need new approaches to stimulate the body’s immune system to control the prostate cancer…We are excited to have the opportunity to explore the potential of ADXS-504 immunotherapy as a novel treatment modality for biochemically recurrent prostate cancer.”

Many patients with prostate cancer experience biochemical recurrence, which occurs due to rising PSA levels following local treatment with radiotherapy or prostatectomy. Patients can experience biochemical recurrence over a prolonged period of time, but it is not often associated with imminent death. As such, treatment strategies that delay the onset of metastatic disease are needed, and avoiding overtreating patients whose disease may never impact their survival or quality of life is another priority.

ADXS-504 is a Listeria monocytogenes (Lm)–based immunotherapy that elicits T-cell responses against 24 tumor antigens that comprise 14 peptide antigens derived from hotspot mutations that frequently occur in patients with prostate cancer, as well as 10 peptide antigens derived from sequence-optimized tumor-associated antigens that are differentially or overexpressed in the disease.

The agent was developed to express several tumor-antigen targets to which patients can potentially produce a broad set of effector T cells that can help control the disease. Additionally, ADXS-504 is expected to induce immune responses followed by adaptive responses and modification of the immunosuppressive tumor microenvironment.

Previously, in January 2020, the FDA gave the green light to the investigational new drug application for ADXS-504, which cleared the way for the agent to proceed to a phase 1 clinical trial2 that is expected to launch later this year.

“We are pleased to be working with Columbia University Irving Medical Center to conduct the first clinical evaluation of ADXS-504 in earlier stages of prostate cancer where drug constructs of this type could potentially control micrometastasis efficiently,” Kenneth A. Berlin, president and chief executive officer of Advaxis, added in the release. “The strategic decision to transition the ADXS-504 to an investigator-sponsored study at Columbia will provide access to world-class expertise and has the potential to accelerate patient recruitment in order to expedite our clinical progress.”

ADXS-504 is a part of Advaxis, Inc.’s ADXS-HOT program, which aims to target hotspot mutations across 10 cancer types.

Another agent in the program, ADXS-PSA, is a live attenuated Lm-listeriolysin O immunotherapy that was bioengineered to produce an antigen adjuvant fusion protein comprised of a truncated fragment of the listeriolysin fused to human prostate-specific antigen.3 The agent is under exploration in combination with pembrolizumab (Keytruda) as part of the phase 1/2 KEYNOTE-046 trial (NCT02325557).

In part A of the trial, the safety and tolerability of the immunotherapy as a single agent was evaluated in patients with progressive metastatic castration-resistant prostate cancer (mCRPC) on androgen deprivation therapy. Here, the investigators also identified the recommended phase 2 dose of the agent in this population for part B of the trial, where they further examined the safety and tolerability of the agent plus pembrolizumab.

For part B, 37 patients were given intravenous (IV) pembrolizumab at 200 mg, followed by IV ADXS-PSA, 1 x 109 CFU every 3 weeks for up to 24 months or until progressive disease or treatment discontinuation.

Secondary end points focused on antitumor activity, overall survival (OS), and progression-free survival with the single agent and the combination.

Results indicated that the combination had activity in patients with mCRPC and could be associated with an improvement in OS, particularly in those with visceral metastasis. In the total population, the median OS with the doublet was 33.7 months (95% CI, 15.4–not reached [NR]). In the 17 patients who did not receive prior docetaxel, the median OS was NR, while it was 16 months in those who received prior docetaxel (n = 20) and 16.4 months in those who had previous visceral metastasis (n = 11). The doublet elicited an objective response rate of 72% (n = 21/29) in evaluable patients who had stable disease.

The combination was safe and tolerable, with most treatment-related toxicities being grade 1 or 2 in severity and including chills/rigors, fever, hypotension, nausea, and fatigue.


  1. Advaxis announces agreement with Columbia University Irving Medical Center to fund phase 1 study of ADXS-504 for the treatment of early prostate cancer. News release. Advaxis, Inc. April 5, 2021. Accessed April 19, 2021.
  2. Advaxis announces FDA clearance of IND for ADXS-504 for treatment of prostate cancer. News release. Advaxis, Inc. January 7, 2020. Accessed April 19, 2021.
  3. Stein MN, Fong L, Mega AE, et al. KEYNOTE (part B): effects of ADXS-PSA in combination with pembrolizumab on survival in metastatic, castration-resistant prostate cancer patients with or without prior exposure to docetaxel. J Clin Oncol. 2020;38(suppl 6):126. doi:10.1200/JCO.2020.38.6_suppl.126