navlimetostat (BMS‐986504) / BMS - LARVOL DELTA

A Study of BMS-986504 Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5) (clinicaltrials.gov) - P2 | N=260 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

Monotherapy • New P2 trial • Oncology • Solid Tumor • MTAP

BMS-986504 in Patients With Homozygous MTAP-Deletion (Del): Clinical Results in Patients With NSCLC Enrolled in CA240-0007 (IASLC-WCLC 2025) - "BMS-986504 was welltolerated with a low rate of hematologic toxicity across all tumors. Theseresults support further investigation of BMS-986504 as a potentialfirst-in-class treatment option for patients with advanced NSCLC with MTAP -del."

Clinical • Anemia • Biliary Cancer • Cholangiocarcinoma • Lung Cancer • Mesothelioma • Neutropenia • Non Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • ALK • EGFR • MTAP

MountainTAP-29: A randomized phase II/III study of first-line (1L) BMS-986504 + pembrolizumab (pembro) + chemotherapy (chemo) in patients (pts) with metastatic NSCLC with homozygous MTAP deletion (MTAP-del) (ELCC 2026) - P2/3 | "In both phases, secondary endpoints include ORR, DCR, and DOR by RECIST v1.1 (phase II, per investigator assessment; phase III, per BICR), and safety. MountainTAP-29 is currently recruiting."

Clinical • IO biomarker • Metastases • P2/3 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • MTAP • PD-L1 • ROS1

Clinical, genomic, and tumor microenvironment (TME) characterization of MTAP-deletion (MTAP-del) in advanced/metastatic NSCLC (ELCC 2026) - "MTAP-del is associated with poor outcomes with 1L PEMBRO + chemo, independent of PD-L1 status, and a cold TME. These results support investigation of MTA-cooperative PRMT5 inhibitors, including BMS-986504, in this pt population and in the ongoing MountainTAP-9 and MountainTAP-29 studies.Editorial acknowledgement Medical writing and editorial support for the development of this abstract, under the direction of the authors, was provided by Samantha L. Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, funded by Bristol Myers Squibb."

Biomarker • Clinical • IO biomarker • Metastases • Tumor microenvironment • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDKN2A • EGFR • MTAP • PD-L1

CA240-0029: A Study of BMS-986504 in Combination with Pembrolizumab Plus Chemotherapy Versus Placebo Plus Pembrolizumab and Chemotherapy in First-line Metastatic Non-small Cell Lung Cancer with Homozygous MTAP Deletion (clinicaltrialsregister.eu) - P2/3 | N=191 | Recruiting | Sponsor: Bristol-Myers Squibb Services Unlimited Company

New P2/3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

A phase 0/1 study of PRMT5 inhibitor BMS-986504 in recurrent glioblastoma participants with MTAP deletion (AACR 2026) - "Abstract is embargoed at this time."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MTAP

BMS-986504 with or without gemcitabine (GEM) + nab-paclitaxel (nab-P) in patients (pts) with pancreatic ductal adenocarcinoma (PDAC) and homozygous MTAP deletion (MTAP-del) from CA240-0007 (ESMO-TAT 2026) - P1 | "BMS-986504 monotherapy showed durable antitumor activity and was well tolerated in pts with heavily pretreated advanced PDAC. Initial data of BMS-986504 + GEM + nab-P showed promising antitumor activity and manageable safety, supporting further evaluation of BMS-986504 in pts with MTAP-del PDAC. Two additional escalating dose cohorts in CA240-0007 SS3 and the phase 2/3 MountainTAP-30 study of BMS-986504 + GEM + nab-P are enrolling."

Clinical • Oncology • Pancreatic Ductal Adenocarcinoma • MTAP

MTAP Loss Is Frequent in Oncogene-Driven NSCLC and May Confer Sensitivity to Combined PRMT5 Inhibitors and Targeted Therapies. (PubMed, Ann Oncol) - "MTAP loss is frequent in oncogene-driven NSCLC, particularly in ALK-, RET-, and EGFR-altered subtypes. MTA-cooperative PRMT5 inhibition demonstrates broad activity in MTAP-deleted, oncogene-driven models and, and may enhance targeted therapy efficacy in selected settings."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CDKN2A • EGFR • MTAP

Impact of MTAP Deletion on Immunotherapy Outcomes in Patients with Mesothelioma (IASLC-TTLC 2026) - "MTAPdel was found in 21% of DPM tumors and was associated with worse OS, underscoring the need to enhance IO efficacy for these patients. Given pre-clinical evidence for synergy between PRMT5 inhibition and IO, we are opening a clinical trial examining the addition of the PRMT5 inhibitor BMS-986504 with ipilimumab/nivolumab in the first-line treatment of MTAPdel DPM, as well as to standard-of-care treatments in other MTAPdel advanced solid tumors."

Clinical • IO biomarker • Lung Cancer • Solid Tumor • BAP1 • CDKN2A • LATS2 • MTAP • NF2 • SETD2 • TP53

Phase 1b Trial of BMS-986504 in Combination With Olaparib in Patients With MTAP Loss (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: Jun 2026 ➔ Feb 2026

Enrollment open • Trial initiation date • Oncology • Solid Tumor • MTAP

CA240-0030: A study of BMS-986504 in combination with Nab-p/Gem versus placebo in combination with Nab-p/Gem in untreated metastatic PDAC with homozygous MTAP deletion (clinicaltrialsregister.eu) - P2/3 | N=162 | Recruiting | Sponsor: Bristol-Myers Squibb Services Unlimited Company

New P2/3 trial • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • MTAP

A Phase II Study Evaluating BMS-986504 in MTAP-deleted Pancreatic Cancer (clinicaltrials.gov) - P2 | N=60 | Suspended | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Suspended

Trial suspension • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MTAP

Clinical Collaborations (GlobeNewswire) - "Under a collaboration with Summit Therapeutics, Inc., the APEX-103 trial is evaluating Revolution Medicines’ RAS(ON) inhibitors with ivonescimab, Summit’s PD-1/VEGF bispecific antibody, across multiple solid tumor settings. The first patient was recently dosed in this clinical trial....The company also recently entered into a clinical collaboration with Bristol Myers Squibb to evaluate daraxonrasib in combination with navlimetostat, Bristol Myers Squibb’s MTA-cooperative PRMT5 inhibitor, in patients with pancreatic cancer whose tumors carry both a RAS mutation and MTAP deletion."

Licensing / partnership • Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

Phase 1b Trial of BMS-986504 in Combination With Olaparib in Patients With MTAP Loss (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Oncology • Solid Tumor • MTAP

BMS-986504 in patients (pts) with advanced solid tumors with homozygous MTAP deletion (MTAP-del): Clinical update and first report of pharmacokinetics (PK) and pharmacodynamic (PD) analyses from CA240-0007. (ASCO 2025) - P1 | "With longer f/u, BMS-986504 continued to show increasingly durable antitumor activity. BMS-986504 demonstrated a favorable PK/PD profile, supporting QD dosing at 400 and 600 mg. These results support further investigation of BMS-986504 at 400 and 600 mg QD as a potential first-in-class synthetic lethal Tx option in pts with advanced solid tumors with MTAP-del."

Clinical • Metastases • PK/PD data • Biliary Cancer • Cholangiocarcinoma • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

A phase 2/3 randomized study of BMS-986504 with nab-paclitaxel (nab-P) and gemcitabine (GEM) in first-line (1L) metastatic pancreatic ductal adenocarcinoma (PDAC) with homozygous MTAP deletion (MTAP-del): MountainTAP-30. (ASCO-GI 2026) - P2/3 | "Secondary endpoints include ORR, DCR, duration of response, and time to response by RECIST v1.1. MountainTAP-30 is currently recruiting."

Clinical • First-in-human • Metastases • P2/3 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • MAT2A • MTAP

MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario. (PubMed, Cancer Res) - "MTA-cooperative PRMT5 inhibitors such as BMS-986504/MRTX1719 and AMG 193 target the PRMT5-MTA complex, while inhibitors of the SAM synthetase methionine adenosyl transferase 2A (MAT2A), such as IDE397, deprive PRMT5 of its methyl donor SAM. In this review article, we summarize the mechanisms of action, preclinical data, and clinical data available thus far for these novel classes of oncology precision medicine and discuss potential future directions relevant to MTAP deletion as a promising synthetic lethal vulnerability for cancer therapy."

Journal • Hematological Disorders • Oncology • MAT2A • MTAP

A Phase II Study Evaluating BMS-986504 in MTAP-deleted Pancreatic Cancer (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Oncology • Pancreatic Cancer • Solid Tumor

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors, including glioblastoma, with MTAP loss (SNO 2025) - P1/2 | "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 were the first MTA-cooperative PRMT5 inhibitors entered in clinical trials for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant in preclinical species. TNG456 is currently enrolling patients with MTAP-null solid tumors, including glioblastoma, in a Phase 1/2 clinical study (NCT06810544). With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including glioblastoma and CNS metastases."

Brain Cancer • Glioblastoma • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

A phase 0/1 study of PRMT5 inhibitor BMS-986504 in recurrent glioblastoma participants with MTAP deletion. (SNO 2025) - P1 | "This study presents the first PK/PD evidence of PRMT5 inhibition in infiltrative GBM. The Phase 0/1 trial marks a critical step toward leveraging synthetic lethality in MTAP-deleted GBM."

Brain Cancer • Glioblastoma • Solid Tumor • CASP3 • MTAP

Clinical Significance of MTAP Deletions and their Overlap with Concurrent Oncogenic Driver Alterations Including EGFR in Non-Small Cell Lung Cancer. (PubMed, J Thorac Oncol) - "MTAP dels frequently co-occur with oncogenic driver alterations and can develop at time of osimertinib resistance. A patient with oncogenic driver-positive, MTAP-del NSCLC had a partial response to PRMT5 inhibitor treatment. This work could inform future trials of PRMT5 and MAT2A inhibitors."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDKN2A • EGFR • MAT2A • MTAP

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors, including glioblastoma, with MTAP loss (WFNOS 2025) - P1/2 | "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 were the first MTA-cooperative PRMT5 inhibitors entered in clinical trials for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant in preclinical species. TNG456 is currently enrolling patients with MTAP-null solid tumors, including glioblastoma, in a Phase 1/2 clinical study (NCT06810544). With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including glioblastoma and CNS metastases."

Brain Cancer • Glioblastoma • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • MTAP

­A phase 0/1 study of PRMT5 inhibitor BMS-986504 in recurrent glioblastoma participants with MTAP deletion. (WFNOS 2025) - P1 | "This study presents the first PK/PD evidence of PRMT5 inhibition in infiltrative GBM. The Phase 0/1 trial marks a critical step toward leveraging synthetic lethality in MTAP-deleted GBM."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CASP3 • MTAP

A Study to Assess Safety, Tolerability and Drug Levels of BMS-986504 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Solid Tumor

CA240-0007: Phase 1 Study of MRTX1719 in Solid Tumors With MTAP Deletion (clinicaltrials.gov) - P1 | N=336 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Apr 2026 ➔ Dec 2027 | Trial primary completion date: Apr 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Brain Cancer • Lung Cancer • Mesothelioma • Neurofibrosarcoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MTAP