Jennifer Carlisle, MD

Preliminary results from a safety and tolerability phase I/II study (NCT03847519) signal promise for ADXS-503 alone and in combination with pembrolizumab (Keytruda) as treatment of patients with metastatic squamous and non-squamous nonsmall cell lung cancer (NSCLC), Advaxis, Inc, announced in a press release. Findings were presented by Jennifer Carlisle, MD during the International Association for the Study of Lung Cancer 2020 Targeted Therapies of Lung Cancer Meeting, February 19-22, 2020, in Santa Monica, California.

To date, 9 participants out of about 50 patients were dosed with the ADXS-503. Seven patients received ADXS-503 alone, and 2 patients received ADXS-503 in combination with pembrolizumab. Three patients from the monotherapy arm (50%) showed stable disease, as did 1 patient in the combination arm. The patients in the combination arm also had a 25% reduction in a site lesion. A notable finding is that stable disease occurred in patients who were heavily pretreated and had failed up to 6 prior lines of therapy. The majority of patients included in this analysis progressed on prior immunotherapy treatments.

The safety assessment showed no dose-limiting toxicities, and the combination of ADXS-503 and pembrolizumab appeared to be safe and tolerable in heavily pretreated patients with NSCLC. Most of the adverse events (AEs) observed were grades 1 and 2. Toxicities with the combination regimen were not additive to the safety profiles of either drug.

“These data are important given the highly refractory patient population with most evaluated patients progressing on prior immunotherapies and, while early, we are particularly interested in documenting additional potential signals of synergy with Keytruda. We look forward to reporting additional clinical and immunogenicity data later this year in addition to starting part C of the study which will evaluate ADXS-503 in combination with pembrolizumab as a first-line treatment for patients with NSCLC,” said Andres Gutierrez, chief medical officer of Advaxis, in a statement to the press.

The open-label study aims to accrue 74 participants who will be evaluated in 3 arms. The first arm (part A) has been completed. In part A safety phase, patients were given 1e8 colony-forming unit (CFU) of ADXS-503 intravenously (IV), every 3 weeks at dose level one or 5e8 CFU at dose level 2. In the second arm (part B), patients receive an equivalent dose of ADXS-503 in part A plus pembrolizumab 200 mg every 3 weeks for up to 2 years. In part C, which is assessing the efficacy of ADXS-503, patients receive 1e8 CFU plus pembrolizumab 200 mg IV, every 3 weeks for up to 2 years. In all phases of the study, patients continue receiving treatment until disease progression, unacceptable toxicity, or another treatment discontinuation criterion is met.

The coprimary end points of the study are the safety/tolerability of ADXS-503 in part A and B and preliminary anti-tumor activity of ADXS-503 plus pembrolizumab in part C. The key secondary end points include progression-free survival and overall survival.

Patients were eligible for study inclusion given they had a histologically or cytologically confirmed stage IV squamous or non-squamous NSCLC with measurable disease, an ECOG performance status of 0 to 1, a life expectancy of at least 3 months, and adequate organ function. Patients must have recovered from any prior grade 1 AEs and could not have any existing comorbidities or medical conditions that preclude therapy, as determined by the study investigators. Some individuals were excluded from the study due to prior treatments, infections, and comorbidities.

Now that part A is completed, the study is actively accruing patients across five sites in the United States to be treated with ADXS-503 plus pembrolizumab in part B.

Reference:

Advaxis announces positive clinical data in ongoing phase 1/2 ADXS-503 trial in NSCLC at the IASLC 2020 targeted therapies of lung cancer meeting [news release]. Princeton, New Jersey: Advaxis, Inc.; February 20, 2020. https://bit.ly/32fHbOW. Accessed February 21, 2020