On May 14, 2020 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products reported updated clinical and biomarker results from the monotherapy and combination arms of the Company’s ongoing Phase 1/2 study investigating ADXS-503 in patients with non-small cell lung cancer (NSCLC) (Press release, Advaxis, MAY 14, 2020, View Source [SID1234558057]). The trial is evaluating ADXS-503, alone and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy. ADXS-503 is part of the Company’s ADXS-HOT cancer-type specific immunotherapy program which leverages Advaxis’ proprietary Lm technology platform to target hotspot mutations that commonly occur in specific cancer types as well as other proprietary, tumor-associated antigens.

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Key data updates:

Sustained clinical benefit in the combination arm, Part B, in the first two evaluable patients who had previously progressed on KEYTRUDA as last therapy whose best response while on KEYTRUDA was stable disease.
One observed partial response and one response of stable disease with 25% reduction in a target lesion, as confirmed in the radiographic scans at 16 weeks of combination therapy
Responses achieved after immediate prior progression on KEYTRUDA with previous best responses of stable disease suggests ADXS-503 may re-sensitize or enhance response to KEYTRUDA
Preliminary biomarker data from seven patients in monotherapy demonstrates:
Activation of cytotoxic and memory CD8+ and CD4+ T cells
CD8+ T cells generated in all seven patients evaluated
Antigen spreading observed in five of seven patients for epitopes not incorporated in ADXS-503
Part A monotherapy has been completed (n=7) with three out of six (50%) evaluable patients showing stable disease.
As a monotherapy, and in combination with KEYTRUDA, ADXS-503 appeared safe and well tolerated with no dose limiting toxicities at the dose-levels evaluated.
"We are thrilled to see sustained clinical benefit with ADXS-503 in combination with KEYTRUDA in these first two evaluable patients who had recently progressed on KEYTRUDA," said Ken Berlin, Chief Executive Officer of Advaxis. "Importantly these responses were achieved in patients with prior best responses that were limited to stable disease during their two years on this checkpoint inhibitor. Taken together, these results leave us increasingly confident that ADXS-503 has the potential to restore or enhance sensitivity to checkpoint inhibitors. In addition, we believe our recent biomarker data, which shows the robust and specific activation of an immune response to ADXS-503 antigens, provides important understanding and validation of the mechanism of action of ADXS-503."

Dr. Andres Gutierrez, Chief Medical Officer at Advaxis, said, "With these promising clinical, safety and immunogenicity data, we have decided to expand Part B of the study, which will continue evaluating patients that have progressed on KEYTRUDA as their last prior therapy. In addition, we will start Part C of the trial to evaluate ADXS-503 with KEYTRUDA combination therapy as a first line treatment for NSCLC patients that cannot tolerate the standard of care regimen with KEYTRUDA in combination with chemotherapy. With the recent dosing of the third patient in Part B, Dose Level 1 which completes this cohort, we anticipate beginning enrollment in the Part B expansion and Part C in early June and look forward to continued progress as we evaluate the ability of ADXS-503 to generate anti-tumor immune responses in advanced NSCLC patients with significant need for new treatment options."

The Phase 1/2 clinical trial of ADXS-503 is seeking to establish the recommended dose, safety, tolerability and clinical activity of ADXS-503 administered alone and in combination with a KEYTRUDA in approximately 50 patients with NSCLC, in at least five sites across the U.S. The two dose levels with monotherapy in Part A, (1 X108 and 5 X108 CFU) have been completed and Part B with ADXS-503 (1 X108 CFU) in combination with KEYTRUDA is currently closed to enrollment. With preliminary encouraging safety and efficacy results, the Company is planning to expand Part B to additional patients at dose level 1 (1 X108 CFU + KEYTRUDA) with the potential to proceed to dose level 2 (5 X108 CFU + KEYTRUDA) at a later date. In addition, the Company intends to expand the study to Part C, which will evaluate ADXS-503 in combination with KEYTRUDA (1 X108 CFU + KEYTRUDA) as a first line treatment for patients that are medically unfit to receive the standard of care regimen with KEYTRUDA in combination with chemotherapy.

About ADXS-HOT
ADXS-HOT is a program that leverages the Company’s proprietary Lm technology to target hotspot mutations that commonly occur in specific cancer types. ADXS-HOT drug candidates are designed to target acquired shared or "public" mutations in tumor driver genes along with other proprietary cancer-testes and oncofetal tumor-associated antigens that also commonly occur in specific cancer types. ADXS-HOT drug candidates are an off-the-shelf treatment, designed to potentially treat all patients with a specific cancer type, without the need for pretreatment biomarker testing, DNA sequencing or diagnostic testing.