BMS-986504, a first-in-class agent targeting MTAP, demonstrated antitumor activity in heavily pretreated patients with MTAP-deleted non–small cell lung cancer (NSCLC), according to findings from the phase I/II CA240-0007 trial presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC; Abstract OA08.01). Higher response rates were seen among patients with EGFR or ALK alterations who would have been ineligible for immunotherapy, even though these subgroups were smaller, in findings from the dose-escalation and dose-expansion phases of the study among patients with NSCLC.
“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,” stated presenting investigator Pasi A. Jänne, MD, PhD, Director of the Lowe Center for Thoracic Oncology and the Scientific Director of the Belfer Center for Applied Cancer Science at Dana-Farber Cancer Institute. “These results support continued development of this agent.”
Rationale and Study Methods
MTAP deletion occurs in about 10% to 15% of all cancers and in about 27% of all NSCLCs. BMS-986504 was designed to selectively bind to the protein arginine methyltransferase 5 (PRMT5)–methylthioadenosine (MTA) complex while sparing MTAP wild-type cells.
The trial enrolled patients with advanced homozygous MTAP-deleted solid tumors and no available treatment options, including 40 with NSCLC, 12 with mesothelioma, 46 with pancreatic ductal adenocarcinoma, and 12 with cholangiocarcinoma. Treatment with BMS-986504 was evaluated across seven doses from 50 mg to 800 mg during the dose-escalation phase of the study.
Key Study Findings
Among 35 evaluable patients with pretreated, advanced or metastatic NSCLC treated with doses of 200 mg to 800 mg of BMS-986504, responses were reported in 29% of patients. Of these responding patients, four had EGFR-positive disease, two had ALK-positive disease, and one had squamous histology. All responses were partial responses.
The overall disease control rate was 80%. The median duration of overall response was 10.5 months, with a median time to response of 4.3 months.
Most treatment-related adverse events were grade 1 or 2, and 14% of events were grade 3 or higher. Several treatment-related hematologic adverse events were reported to be grade 1 to 3, including anemia in 8% of patients, neutropenia in 7%, and thrombocytopenia in 7%. Serious events were reported in 4% of patients, and 2% of events led to treatment discontinuation, although none were considered to be related to myelosuppression. No treatment-related deaths were observed.
Two studies have been initiated to further investigate the use of BMS-986504 in patients with advanced NSCLC and MTAP deletions.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.
