A first-in-human phase I/Ib study of ATG-037 monotherapy and combination therapy with pembrolizumab in patients with advanced solid tumors: STAMINA-01.

3123 Background: ATG-037 is a highly potent oral small molecule inhibitor of CD73. STAMINA-01 is an open-label, first-in-human, phase 1/1b study (NCT05205109) designed to evaluate the safety, pharmacokinetics, and optimal dosing of ATG-037 as monotherapy and in combination with pembrolizumab in patients with refractory/relapsed solid tumors. Methods: The study successfully completed enrollment of dose escalation of ATG-037 with optional addition of pembrolizumab following two cycles of monotherapy in May 2024. The primary objectives were to evaluate the safety and define the optimal biological dose of ATG-037 as monotherapy and combination treatment. As of 20 January 2025, 43 patients were enrolled across the following doses - 20mg BID (n=3), 60mg BID (n=6), 120mg BID (n=10), 240mg BID (n=6), 400mg BID (n=12) and 600mg BID (n=6). The trial is currently recruiting the second part of the study for dose optimization of upfront combination therapy at two dose levels (120mg BID and 400mg BID). Results: Efficacy: As of the data cut-off (20 Jan 2025), 43 patients were enrolled on study and received monotherapy. While on ATG-037 monotherapy, 21 patients had a best response of stable disease (SD) with a disease control rate (DCR) of 49%. Twenty-eight patients with a history of acquired checkpoint inhibitor resistance received combination therapy; 7 of which (5 melanoma and 2 NSCLC patients) achieved a confirmed partial response (PR) with an overall response rate (ORR) of 25% (95% CI: [51.33, 86.78]). Additionally, 15 patients had a best response of SD with a DCR of 79% (95% CI: [8.30, 40.95]). Of the 11 enrolled melanoma patients who received combination, 5 achieved a PR for an ORR of 45% and 6 achieved SD for an DCR of 100%. Of the 9 enrolled NSCLC patients who received combination, 2 achieved a PR for an ORR of 22% and 4 achieved SD for an DCR of 67%. Safety: While on monotherapy, 24/43 (56%) patients reported treatment-related adverse events (TRAEs). While on combination therapy, 17/28 (61%) patients reported TRAEs. The majority of TRAEs were grades 1-2. The only dose limiting toxicity was a grade 3 rash which occurred at the monotherapy 400mg BID dose. Only one serious TRAE (grade 3 immune mediated hepatitis) was reported at the data cut-off. Conclusions: In relapsed/refractory solid tumor patients, ATG-037 appears to be well tolerated as monotherapy and in combination with pembrolizumab. The preliminary efficacy data is encouraging and suggests that the combination regimen may provide a new therapeutic option for CPI resistant NSCLC and melanoma patients. Clinical trial information: NCT05205109 .