Preliminary Data from Phase 1 Study Evaluating ADXS-NEO Suggest Rapid Immunogenicity and Clinical Activity

In Clinical Trials by Barbara Jacoby

Provider: Business Wire

From: apnews.com

Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, announces the presentation of ADXS-NEO data in a poster discussion entitled “ Safety and Immunogenicity of a Personalized Neoantigen-Listeria Vaccine in Cancer Patients” at the American Association for Cancer Research (AACR) Annual Meeting underway in Atlanta. The discussion will be held on Sunday, March 31, 2019 from 1:00-5:00 p.m. ET and will be led by J. Randolph Hecht, M.D., Professor of Clinical Medicine, David Geffen School of Medicine at UCLA and Director of the UCLA Gastrointestinal Oncology Program.

ADXS-NEO is a live, attenuated Listeria monocytogenes (Lm) immunotherapy, using personalized antigen delivery based on whole-exome sequencing of a patient’s tumor to identify personal neoantigens. The ongoing Phase 1 trial is designed to evaluate the safety, tolerability and preliminary clinical immunological activity of ADXS-NEO alone (Part A) and in combination with anti-PD-1 antibody therapy (Part B) in subjects with certain types of advanced or metastatic solid tumors. Part C of the trial will be an expansion of the combination therapy arm and will be initiated based on emerging data from the first two parts of the trial.

Preliminary findings from the ADXS-NEO Phase 1 study include the following:

  • Substantial anti-tumor immunity, including T cell responses to neoantigens and antigen spreading, was observed within one week of first dose at both dose levels
  • Dosing of ADXS-NEO at 1×10 8 colony forming units (CFU) has been well-tolerated in two patients
  • ADXS-NEO dosed at 1×10 9 CFU was beyond the maximum tolerated dose (MTD)
    • Reversible Grade 3 hypoxia (n=2) and Grade 3 hypotension (n=1) were dose-limiting toxicities (DLTs)
  • Manufacturing of ADXS-NEO, comprised of 40 personal neoantigens, was successfully completed within seven to eight weeks for each subject

“Advaxis’ ADXS-NEO is a novel, personalized vaccine encoding mutations specific to an individual patient’s tumor designed to induce anti-cancer immunity. Four patients have been evaluated across two dose levels thus far in this ongoing clinical trial. While dose level 1 (1×10 9 CFU) was determined to be above the MTD, dose level -1a (1×10 8 CFU) has been safe and well tolerated in two patients treated to date, with primarily Grade 1 and Grade 2 chills, fever and tachycardia. Substantial immunological activity was observed across both dose levels, including rapid neoantigen-specific CD8+ T cell generation, which is essential for potential clinical benefit. We look forward to the planned combination therapy arm with checkpoint inhibitors,” said Dr. Hecht.

“The patients being evaluated for safety and tolerability in Part A all have late-stage disease and have been treated with numerous prior therapies. As a result, we did not expect to observe significant clinical activity in this cohort,” said Andres Gutierrez, M.D. Ph.D., Chief Medical Officer of Advaxis. “Nevertheless, we have seen some encouraging clinical signals to date, including one patient at dose level 1 with non-small cell lung cancer who achieved stable disease after only two doses of ADXS-NEO, which is consistent with rapid immune activation.” He concluded, “This is the first presentation of clinical data from our ADXS-NEO program at a major medical conference. We are continuing to enroll subjects and gather additional clinical and immune correlative data, and plan to share updated data from this study throughout this year.”

The full abstract is available at www.advaxis.com and the poster will be available on the Company’s website on Sunday, March 31, 2019 at 1:00 p.m. ET.

About ADXS-NEO

ADXS-NEO is an investigational personalized Lm- based immunotherapy designed to generate immune response against mutation-derived tumor-specific neoantigens identified through DNA sequencing of a patient’s own tumor. The program focuses on creating a customized treatment for each patient targeting multiple neoantigens found in a biopsy of the patient’s tumor.

About Advaxis, Inc.

Advaxis, Inc. is a late-stage biotechnology company focused on the discovery, development and commercialization of proprietary  Lm -based antigen delivery products. These immunotherapies are based on a platform technology that utilizes live attenuated Listeria monocytogenes ( Lm ) bioengineered to secrete antigen/adjuvant fusion proteins. These  Lm -based strains are believed to be a significant advancement in immunotherapy as they integrate multiple functions into a single immunotherapy and are designed to access and direct antigen presenting cells to stimulate anti-tumor T cell immunity, activate the immune system with the equivalent of multiple adjuvants, and simultaneously reduce tumor protection in the tumor microenvironment to enable T cells to eliminate tumors. Advaxis has four programs in various stages of clinical development: ADXS-HPV for cervical cancer; ADXS-NEO, a personalized neoantigen-directed therapy for multiple cancers; ADXS-503 for non-small cell lung cancer, from its ADXS-HOT off-the-shelf neoantigen-directed program; and ADXS-PSA for prostate cancer.