A phase I study of ADXS-503 alone and in combination with pembrolizumab in subjects with metastatic squamous or non-squamous non-small cell lung cancer (NSCLC).

e21682 Background: ADXS-503 (A503) is an off-the-shelf, attenuated Listeria monocytogenes (Lm)-based immunotherapy bioengineered to elicit potent T cell responses against 22 tumor antigens commonly found in NSCLC (i.e., 11 hotspot mutations and 11 tumor-associated antigens, TAAs). Pembrolizumab (Pembro) is a programed death receptor-1 (PD-1)- blocking antibody with proven efficacy in NSCLC. A503 and Pembro have complementary mechanisms of immune activation and reversal of immune tolerance. Methods: This is a phase I study of A503 ± Pembro in patients (pts) with metastatic squamous or non-squamous NSCLC. Dose escalation with A503 alone has been tested at two dose levels (i.e., 1 and 5 x10 8 CFU) in Part A in pts refractory or intolerant to prior systemic therapy. In dose escalation Part B, A503 is being evaluated at the same dose levels (DLs) in combination with Pembro in pts with disease progression on Pembro. Part C will be a dose expansion cohort with A503 + Pembro as first-line treatment in the metastatic setting. A503 ± Pembro (200 mg) will be infused intravenously every 3 weeks until disease progression or limiting toxicity. Main endpoints include safety, tolerability and immune-correlative data. Results: Nine patients have been treated: 7 with A503-alone in Part A and two pts with A503+ Pembro in Part B-DL1. No pts in Part A experienced dose-limiting toxicities at the 2 DLs tested. Two Grade 3 adverse events occurred in one pt related to the infusion: hypertension and flu-like syndrome. A transient and manageable SAE (Grade 2 acute kidney injury) was possibly related to A503 alone at 5 x10 8 CFU. A503+ Pembro have been well tolerated in 2 pts in Part B-DL1. Four pts achieved a best overall response of stable disease, three in Part A and one in Part B. A503 alone induced immune responses in pts so far evaluated in Part A. Conclusions: ADXS-503 alone has demonstrated a manageable safety profile and immune responses in Part A. The 1x10 8 CFU was identified as the recommended phase II dose. Dose escalation with A503+ Pembro is ongoing and dose expansion in first line treatment is due to start shortly. Clinical trial information: NCT03847519.