A phase I study of nelmastobart (hSTC810), an anti-BTN1A1 antibody, in patients with advanced solid tumors.

Abstract

2633 Background: Butyrophilin 1A1 (BTN1A1) is a novel immune checkpoint that is primarily expressed by tumor cells in a manner that is mutually exclusive with PD-(L)1. BTN1A1 can potentially be targeted to extend new immunotherapeutic treatment options to patients (pts) whose tumors are unresponsive to anti-PD-(L)1 therapy. This phase I study describes the safety and clinical activity of Nelmastobart (hSTC810), a humanized monoclonal antibody targeting BTN1A1, in pts with advanced solid tumors. Methods: Nelmastobart was administered intravenously every 2 weeks across 6 dose levels from 0.3 mg/kg to 15 mg/kg. The primary objectives were to determine the safety profile and maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Using a 3+3 design, dose-escalation cohorts were evaluated for dose-limiting toxicities (DLT) during the first 2 cycles. Backfill cohorts were allowed once a dose was deemed safe. Response was assessed using RECIST 1.1 every 4 cycles (8 weeks). Pts were treated until disease progression or unacceptable toxicity. Results: As of January 30, 2023, enrollment in the dose-escalation cohorts is complete. A total of 39 pts with colon (n=14), lung (NSCLC n=3; SCLC n=2), urothelial (n=3), breast, cholangiocarcinoma, melanoma, ovarian, pancreatic (n=2) each, adrenocortical, anal, esophageal, H&N, PEComa, skin, and thymic (n=1) cancers each were treated in the dose-escalation and backfill cohorts. Median duration of therapy for all pts was 8 weeks (maximum 29 weeks). Most common treatment related adverse events (TRAEs) reported were grade 1-2 fatigue (6%), headache (5.9%), and nausea (4.4%); furthermore, there were no TRAEs ≥ 3. No pts was discontinued or required dose reduction due to TRAEs. There were no DLTs across all dose levels and the MTD was not reached. In evaluable pts, one confirmed partial response was observed in MSI-H colon cancer (3 mg/kg) and 13 pts (colon, H&N, lung, melanoma, ovarian, thymic carcinoma) had a best response of stable disease (SD) across multiple dose levels. Median duration of PR/SD pts on study was 17.5 weeks. Interim pharmacokinetics (PK) analysis demonstrated consistent exposure with linear PK. Pharmacodynamic analysis measuring cytokines and cell-based markers is pending and will be presented. Based on the safety, efficacy, and PK, we recommend 15 mg/kg Q2W as the RP2D. Conclusions: Nelmastobart is well-tolerated without DLTs up to the final dose of 15 mg/kg. Current data show evidence of anti-tumor activity and durable SD. Clinical development planning for a phase Ib/II clinical trial is underway to further characterize the therapeutic dose and efficacy in select solid tumors. Clinical trial information: NCT05231746 .