997MO - 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

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) evaluating the safety, pharmacokinetics, and optimal dose of ATG-037 as a monotherapy, or in combination with pembrolizumab, in patients with refractory/relapsed solid tumors.

Methods

The study is currently in dose escalation of the ATG-037 with optional addition of pembrolizumab following two cycles of monotherapy. The primary objectives are to evaluate the safety and define the optimal biological dose of ATG-037 as monotherapy and in combination with pembrolizumab. As of 29 February 2024, 32 patients enrolled at the following levels – 20mg BID (n=3), 60mg BID (n=6), 120mg BID (n=8), 240mg BID (n=6), 400mg BID (n=6) and 600mg BID (n=3). The sixth dose level of 600mg BID is still enrolling at the data cut-off.

Results

At the data cut-off (29 Feb 2024), 32 patients received ATG-037 monotherapy; 14 had a best response of stable disease (SD) with a disease control rate (DCR) of 43.8%. Twenty patients with a history of acquired checkpoint inhibitor (CPI) resistance received combination therapy; 3 patients (2 with melanoma and 1 with NSCLC) achieved a confirmed partial response (PR) and 1 patient with NSCLC achieved an unconfirmed PR with an ORR of 20% (95% CI: [0.0573, 0.4366]). Additionally, 9 patients had a best response of SD and the DCR was 65%. Of the patients on monotherapy, 13/32 (40.6%) reported treatment-related adverse events (TRAEs). Of the patients who received the combination, 5/20 (25.0%) reported TRAEs. At the 400mg BID level, one patient experienced a dose-limiting toxicity grade 3 rash while on monotherapy; all other TRAEs were grades 1-2. No treatment-related serious adverse events were reported as 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 identification

NCT05205109.

Editorial acknowledgement

Legal entity responsible for the study

Antengene.

Funding

Antengene.

Disclosure

G. Kichenadasse: Financial Interests, Advisory Board: Antengene. J. Lombard: Financial Interests, Personal, Advisory Board, Ad Board for durvalumab + olaparib in uterine cancer: AstraZeneca; Financial Interests, Personal, Invited Speaker, educational dinner talk June 2023: Novartis; Financial Interests, Personal, Other, registration for virtual ESMO attendance October 2023: Novartis; Financial Interests, Personal, Invited Speaker, Speaker educational dinner March 2023: Eisai; Financial Interests, Personal, Invited Speaker, educational dinner speaker: Giliead; Financial Interests, Personal, Other, Ad Board for durvalumab + olaparib in uterine cancer: GSK. M.A.A. Khattak: Financial Interests, Advisory Board: Antengene. A. Kudva, H. Cui, E. Hoe: Financial Interests, Full or part-time Employment: Antengene. K.P. Lynch: Financial Interests, Personal, Other, Consultant: Antengene; Financial Interests, Personal, Stocks/Shares, share options awarded as part of previous employment with company: Antengene; Other, Previously employed as CMO to the company, now working as consultant: Antengene. M. Chisamore: Financial Interests, Institutional, Full or part-time Employment: Merck & Co. Inc; Financial Interests, Institutional, Stocks/Shares: Merck & Co. Inc. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, BeiGene, Hengrui, Merck, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda, Amgen, Daiichi Sankyo; Financial Interests, Coordinating PI: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merck, MSD, Pfizer, Roche, Eli Lilly; Financial Interests, Steering Committee Member: Sanofi, Yunhan; Non-Financial Interests, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Other, Editorial Board member of Ann Oncology and ESMO Open: ESMO. All other authors have declared no conflicts of interest.