Excellent CBR and prolonged PFS in non-squamous NSCLC with oral CA-170, an inhibitor of VISTA and PD-L1

Abstract

Abstract Background VISTA and PD-1/PD-L1 are independent immune checkpoints. Preclinical studies demonstrate synergism with dual blockade of these pathways. CA-170 is an oral agent targeting both VISTA and PD-L1. A Phase I dose escalation study (NCT02812875) has shown acceptable safety up to 2400\xa0mg total daily dosage. Early results from current Phase II have been presented previously (Proc. SITC 2018; P715). Methods The current phase II randomized patients with multiple tumor types (Head & Neck Cancer, Squamous-NSCLC, Non-Squamous-NSCLC, MSI-H+ solid tumors and Hodgkin Lymphoma) to 400mg versus 800mg. Key eligibility included: age ≥ 18 years, ECOG ≤1, adequate organ function, no previous exposure to IO agents and 1-3 lines of prior therapy. Primary objective is response rate assessment by a central radiologist. Secondary endpoints include additional efficacy and safety endpoints. Results The study enrolled 62 IO-naive patients over 8 months, from February through October 2018. Efficacy population included 15 non-squamous NSCLC patients, who had received a median of 2 lines of prior therapy. Additionally, median time from diagnosis was ∼ 14 months, and much higher than 8-9 months in earlier 2nd line IO antibody trials in NSCLC. Eight and seven patients, respectively, received 400 and 800\xa0mg. Demographics and baseline characteristics of both groups are similar. While none of the non-squamous NSCLC patients achieved 30% cut-off for response by RECIST, six had tumor reductions, up to 20%. Analyzed by dose groups, CBR and median PFS were 75% and 19.5 weeks in the 400\xa0mg group versus 50% and 7.9 weeks in the 800\xa0mg group. Superior efficacy at 400mg was also observed in other tumor types. The AEs and SAEs have been as expected without any concerns or major events. Conclusions Excellent CBR and PFS have been observed at 400\xa0mg. Superior effects at 400\xa0mg versus 800\xa0mg dosage may likely be due to a bell-shaped response curve, previously noted in pre-clinical studies with possible activation-induced T cell death at higher doses. CA-170 also appears to have significant safety benefit, compared to IO antibodies. These data position oral IO agents such as CA-170 for evaluation in adjuvant and/or maintenance settings in non-squamous NSCLC. Legal entity responsible for the study Aurigene Discovery Technologies Limited. Funding Aurigene Discovery Technologies Limited. Disclosure All authors have declared no conflicts of interest.