On May 26, 2022 Advaxis, Inc. (OTCQX: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported the publication of updated results from the clinical trial of the lead asset from its ADXS-HOT off-the-shelf, cancer-type specific, immunotherapy program (Press release, Advaxis, MAY 26, 2022, View Source [SID1234615156]).

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These results from the clinical study ADXS-503-101 evaluating the ADXS-503 construct, which is designed to target certain cancers’ commonly occurring hotspot mutations and other tumor-associated antigens, will be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting to be held on June 4-7, 2022, along with the trial design of the study of the second construct from the ADXS-HOT program, ADXS-504.

The goals of this Phase 1/2 open-label trial are to evaluate safety, tolerability, antitumor activity and immune-correlative data of ADXS-503 administered in combination with KEYTRUDA in patients with metastatic NSCLC. In Part B of this study, ADXS-503 is added-on to KEYTRUDA within 12 weeks of the first scan showing disease progression following treatment with KEYTRUDA. In Part C, both drugs are administered to previously untreated patients. The study design of the Phase 1 investigator-sponsor study of ADXS-504 for patients with biochemically recurrent prostate cancer at Columbia University, Herbert Irving Comprehensive Cancer Center NYC, will also be presented.

Key presentation highlights:

Poster Title: "A phase 2 study of an off-the-shelf, multi-neoantigen vector (ADXS-503) in patients with metastatic non-small-cell lung cancer either progressing on prior pembrolizumab or in the first-line setting"
Presenter: Gregory J. Gerstner, M.D., Illinois Cancer Care
Session Type: Poster Session – Hall A
Session Title: "Lung Cancer—Non-Small Cell Metastatic"
Date and Time: June 6, 2022, 8-11 AM (CDT)

Key study characteristics and takeaways:

Part B: 14 patients failing pembrolizumab as last therapy have been treated with ADXS-503 + pembrolizumab (Dose Level 1) with all patients evaluable for safety and efficacy
Overall response rate (ORR) was 14% (2/14) and Disease Control Rate (DCR) was 36% (5/14)
Two durable partial responses (PR) sustained for over 9 months and 21 months, respectively
Three durable cases of stable disease (SD) lasting for over 3, 5 and 14 months, respectively
Patients who seem to achieve clinical benefit in Part B of the study include those with PD-L1 expression ≥ 50% and those with prior pembrolizumab monotherapy exposure ≥ 12 months and/or with DCR > 6 months
Part C: 3 patients have received ADXS-503 + pembrolizumab in the 1st-line metastatic setting with all patients evaluable for safety and efficacy
Data continue to show a DCR of 67% (2/3) in the first three evaluable patients in Part C
Poster Title: "Immunogenicity and disease control induced by a multi-neoantigen vaccine (ADXS-503) in patients with metastatic non-small-cell lung cancer who have progressed on pembrolizumab"

Presenter: Dr. Aaron E. Lisberg, M.D., UCLA
Session Type: Poster Session – Hall A
Session Title: "Lung Cancer—Non-Small Cell Metastatic"
Date and Time: June 6, 2022, 8-11 AM (CDT)

Key takeaways: Long-term follow up of immune correlative markers suggest that ADXS-503 leads to durable clinical benefit in select patients through:

the production of cytokines with periodic pro-inflammatory and anti-tumoral effects supporting innate and adaptive immunity
the activation of Natural Killer (NK) cells in tumor control
the induction of proliferation and activation of previously exhausted CD8+ T-cells facilitating reaction to hotspot mutation antigens, tumor associated antigens (TAAs), and antigen spreading.
The activation of various subsets of memory CD8+ T cells
Poster Title: "A phase I study of ADXS-504, a cancer type specific immunotherapy, for patients with biochemically recurrent prostate cancer"

Presenter: Karie Runcie, M.D., Columbia University
Session Type: Poster Session – Hall A
Session Title: "Trials in Progress"
Abstract Number: TPS5115
Date and Time: June 6, 2022, 1:15-4:15 CDT (CDT)

"The correlation of durable clinical benefit with long-term immunological surveillance data from Part B of the ADXS-503 study is extremely encouraging," said Ken Berlin, President and CEO of Advaxis. "We not only observe a competitive ORR by adding-on ADXS-503 in patients failing pembrolizumab, but we also now better understand how ADXS-503 may reverse the exhaustion or enhance the activity of pembrolizumab in these cases," he concluded. "The immunogenicity studies tend to demonstrate that ADXS-503 does more than just activate antigen-specific T cells as part of the adaptive response in Part B patients. The clinical benefit may also be derived from the serial elevation of certain serum cytokines throughout the course of therapy as well as from the activation of NK and induction of memory T cells. These pleotropic effects of Lm vectors, which had been documented in preclinical models and now shown in the ADXS-503 trial, help to differentiate ADXS-503 from other vaccine platforms," added Andres Gutierrez, EVP and Chief Medical Officer of Advaxis. "Importantly, those effects are induced safely and without the use of adjuvant agents," he concluded.

Enrollment in Part B will continue up to a total of 18 patients to further evaluate if ADXS-503 is able to achieve ORR of ≥20% in patients progressing on pembrolizumab therapy, while Part C may enroll up to 25 patients.