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BMS-986504, a first-in-class methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) concentrating on agent, confirmed promising antitumor exercise in closely pretreated sufferers with MTAP-deleted non-small cell lung most cancers (NSCLC), in accordance with outcomes from the Part I CA240-0007 trial offered on the Worldwide Affiliation for the Examine of Lung Most cancers 2025 World Convention on Lung Most cancers (WCLC).
MTAP, encoding the enzyme methylthioadenosine phosphorylase, is poor in lots of cancers. MTA is a byproduct of mobile metabolism that builds up in most cancers cells with a selected deletion: the MTAP gene.
When MTAP is deleted (MTAP-deleted cancers), MTA accumulates and binds to PRMT5, an enzyme that performs a job in cell regulation and survival. BMS-986504 is designed to selectively goal and inhibit PRMT5 when it is certain to MTA (PRMT5-MTA complicated), resulting in cell demise in MTAP-deleted most cancers cells.
The research enrolled sufferers with superior stable tumors harboring homozygous MTAP deletions, a genetic alteration that happens in 10–15% of all cancers, and NSCLC represents as much as 27% of sufferers with MTAP-del.
Amongst clinically evaluable sufferers within the NSCLC cohort (n=35), BMS-986504 demonstrated a 29% general response price (ORR) and a 80% illness management price. Two further sufferers had unconfirmed responses and had been awaiting confirmatory scans. Responses included sufferers 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,” stated Dr. Pasi Jänne of Dana-Farber Most cancers Institute, who offered the findings.
“These results support continued development of this agent.”
Dr. Jänne reported some further key findings:
Responses had been seen in 4/7 EGFR-positive, 2/4 ALK-positive, and 1/3 squamous sufferers.
Median period 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 stated that BMS-986504 was nicely tolerated, with most treatment-related opposed occasions (TRAEs) being grade 1 or 2; 14% of stable tumor sufferers skilled grade ≥3 TRAEs. Hematologic toxicity charges had been low and manageable with sufferers experiencing treatment-related anemia (8%), neutropenia (7%), and thrombocytopenia (7%).
The research included stable tumor sufferers with nearly all of sufferers with NSCLC, mesothelioma, pancreatic ductal adenocarcinoma (PDAC), and cholangiocarcinoma. In accordance with Dr. Jänne, no new security indicators had been noticed throughout tumor varieties.
These outcomes assist additional investigation of BMS-986504 and there are two research for sufferers with superior NSCLC with MTAP-del:
A Multicenter, Randomized, Open-label, Part II Examine Evaluating the Security and Efficacy of BMS-986504 Monotherapy in Contributors With Superior or Metastatic Non-small Cell Lung Most cancers (NSCLC) With Homozygous MTAP Deletion After Development on Prior Therapies—NCT06855771
A Randomized Part II/III Examine of BMS-986504 in Mixture With Pembrolizumab and Chemotherapy Versus Placebo Plus Pembrolizumab and Chemotherapy in First-line Metastatic Non-small Cell Lung Most cancers Contributors With Homozygous MTAP Deletion—NCT07063745
Supplied by
Worldwide Affiliation for the Examine of Lung Most cancers
Quotation:
BMS-986504 demonstrates sturdy responses in MTAP-deleted NSCLC, together with EGFR and ALK-positive tumors (2025, September 8)
retrieved 8 September 2025
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