Antennova's ATN-037 Shows Promise in Checkpoint Inhibitor-Resistant Cancers
核心洞察
Antennova (搜索) presented Phase I/Ib data for ATN-037, a CD73 (搜索) inhibitor, at ESMO 2024, demonstrating its potential to overcome resistance to checkpoint inhibitors.
In NSCLC and melanoma (搜索) patients resistant to CPIs, ATN-037 combined with pembrolizumab showed an overall response rate of 21.1% and a disease control rate of 89.5%.
The Phase I dose escalation study suggests ATN-037 can reverse resistance to anti-PD-1 therapies, warranting further investigation in Phase II trials.
Antennova (搜索) presented encouraging data for its CD73 (搜索) inhibitor, ATN-037, at the European Society of Medical Oncology (ESMO) Congress 2024, highlighting its potential to reverse resistance to checkpoint inhibitors (CPIs) in patients with non-small cell lung cancer (搜索) (NSCLC) and melanoma (搜索). The Phase I/Ib STAMINA-01 study evaluated ATN-037 as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors.
ATN-037 Efficacy in CPI-Resistant Tumors
The study enrolled 43 patients, with 26 having acquired resistance to CPIs and receiving ATN-037 in combination with pembrolizumab. As of July 26, 2024, efficacy data from 19 evaluable patients with NSCLC or melanoma (搜索) showed an overall response rate (ORR) of 21.1% (4/19) and a disease control rate (DCR) of 89.5% (17/19). Specifically, 2 patients with NSCLC and 2 with melanoma achieved confirmed partial responses (PR).
Safety and Tolerability Profile
The safety profile of ATN-037 was also encouraging. While all 43 patients experienced treatment-emergent adverse events (TEAEs), most were not severe. One dose-limiting toxicity (DLT) of Grade 3 rash was observed at the 400 mg twice-daily (BID) dose. No Grade 5 treatment-related adverse events (TRAEs) were reported.
STAMINA Trial Expansion
Based on these promising results, Antennova (搜索) has initiated the dose optimization and dose expansion portion of the Phase II STAMINA trial in Australia and plans to initiate the study in China at the end of October 2024. This expansion will further evaluate the efficacy and safety of ATN-037 in a larger patient population.
CD73 Inhibition as a Novel Therapeutic Strategy
CD73 (搜索) is an enzyme that converts adenosine monophosphate (AMP) to adenosine, an immunosuppressive molecule in the tumor microenvironment. By inhibiting CD73, ATN-037 aims to reduce adenosine levels, thereby enhancing anti-tumor immune responses, particularly in tumors resistant to checkpoint inhibitors. The combination of ATN-037 with pembrolizumab may offer a new therapeutic option for CPI-resistant NSCLC and melanoma (搜索) patients, addressing a significant unmet medical need.