BMS-986504 demonstrates durable responses in MTAP-deleted NSCLC, including EGFR and ALK-positive tumors

(Press-News.org) Barcelona, Spain (September 8, 2025, Noon CEST / UTC +2  ) — BMS-986504, a first-in-class methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) targeting agent, showed promising antitumor activity in heavily pretreated patients with MTAP-deleted non-small cell lung cancer (NSCLC), according to results from the Phase 1CA240-0007 trial presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer (WCLC).

MTAP, encoding the enzyme methylthioadenosine phosphorylase, is deficient in many cancers. MTA is a byproduct of cellular metabolism that builds up in cancer cells with a specific deletion: the MTAP gene. When MTAP is deleted (MTAP-deleted cancers), MTA accumulates and binds to PRMT5, an enzyme that plays a role in cell regulation and survival. BMS-986504 is designed to selectively target and inhibit PRMT5 when it's bound to MTA (PRMT5-MTA complex), leading to cell death in MTAP-deleted cancer cells.

The study enrolled patients with advanced solid tumors harboring homozygous MTAP deletions, a genetic alteration that occurs in 10-15% of all cancers and NSCLC represents up to 27% of patients with MTAP-del. Among clinically evaluable patients in the NSCLC cohort (n=35), BMS-986504 demonstrated a 29% overall response rate (ORR) and a 80% disease control rate. Two additional patients had unconfirmed responses and were awaiting confirmatory scans. Responses included patients with EGFR and ALK alterations who had progressed on prior TKIs.

“BMS-986504 selectively targets the PRMT5-MTA complex in MTAP-deleted cells while sparing normal tissue, providing a precision approach for a difficult-to-treat patient population,” said Dr. Pasi Jänne of Dana-Farber Cancer Institute, who presented the findings. “These results support continued development of this agent.”

Dr. Jänne reported some additional key findings:

Responses were seen in 4/7 EGFR-positive, 2/4 ALK-positive, and 1/3 squamous patients. Median duration of response: 10.5 months; time to response: 4.3 months. Median follow-up: 11.7 months (95% CI, 4.2–12.4). Dr. Jänne said that BMS-986504 was well tolerated, with most treatment-related adverse events (TRAEs) being grade 1 or 2.  14% of solid tumor patients experienced grade ≥3 TRAEs. Hematologic toxicity rates were low and manageable with patients experiencing treatment-related anemia (8%), neutropenia (7%), and thrombocytopenia (7%).

The study included solid tumor patients with the majority of patients with NSCLC, mesothelioma, pancreatic ductal adenocarcinoma (PDAC), and cholangiocarcinoma. According to Dr. Jänne, no new safety signals were observed across tumor types.

These results support further investigation of BMS-986504 and there are 2 studies for patients with advanced NSCLC with MTAP-del:

A Multicenter, Randomized, Open-label, Phase 2 Study Evaluating the Safety and Efficacy of BMS-986504 Monotherapy in Participants With Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) With Homozygous MTAP Deletion After Progression on Prior Therapies - NCT06855771 A Randomized Phase 2/3 Study of BMS-986504 in Combination With Pembrolizumab and Chemotherapy Versus Placebo Plus Pembrolizumab and Chemotherapy in First-line Metastatic Non-small Cell Lung Cancer Participants With Homozygous MTAP Deletion - NCT07063745 About the IASLC:

The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.

About the WCLC:

The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians, and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc.iaslc.org/.

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