navlimetostat (BMS-986504) / BMS - LARVOL DELTA

CA240-0009: A Study of Navlimetostat (BMS-986504) Alone or in Combination With Izalontamab Brengitecan in Participants With Pre-treated Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) With Homozygous MTAP Deletion or MTAP Loss (MountainTAP-9) (clinicaltrials.gov) - P2 | N=182 | Recruiting | Sponsor: Bristol-Myers Squibb | N=130 ➔ 182

Enrollment change • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MTAP

A Phase II Study Evaluating Navlimetostat (BMS-986504) and chemotherapy in resectable/borderline resectable (cohort 1), locally advanced, unresectable (cohort 2), and metastatic (cohort 3) MTAP-deleted Pancreatic Cancer. (ESMO 2026) - No abstract available

Metastases • P2 data • Oncology • Pancreatic Cancer • Solid Tumor • MTAP

A Study of Navlimetostat (BMS-986504) Drug Interactions and Food Effect in Healthy Participants (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

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

SELECT Meso 1 Trial: A Phase II Trial of the MTA-cooperative PRMT5 Inhibitor BMS-986504 in Patients With MTAP-deficient Relapsed Mesothelioma (IASLC-WCLC 2026) - "Deep learning based volumetric tumour analysis will be conducted to support multiomics correlation analysis. Responding patients will have re-biopsies with multiomic analysis at the time of disease progression."

Clinical • P2 data • Mesothelioma • 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

Acquired Resistance to the PRMT5 Inhibitor Confers Collateral Sensitivity to MEK Inhibition in MTAP-Null Non-Small Cell Lung Cancer. (PubMed, Biomolecules) - "Consistently, resistant cells exhibited rewired MAPK-related transcriptional programs. Together, these findings identify MEK inhibition as a reproducible collateral vulnerability associated with acquired MRTX1719 resistance in MTAP-null NSCLC models and support further evaluation of MEK inhibition as a potential treatment-switching strategy following resistance."

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • MTAP

BMS-986504 in Combination With Pemetrexed for the Treatment of Metastatic Solid Tumors With MTAP Deletion (clinicaltrials.gov) - P1/2 | N=72 | Recruiting | Sponsor: Northwestern University | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2027 ➔ Aug 2026

Enrollment open • Trial initiation date • Biliary Cancer • Colon Cancer • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MTAP

A Study to Evaluate the Metabolism, the Routes and Extent of Elimination, and Drug Levels of [14C]Navlimetostat (BMS-986504) in Healthy Female Participants (clinicaltrials.gov) - P1 | N=6 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

Safety and Efficacy of BMS-986504 in Unresectable Malignant Peripheral Nerve Sheath Tumor (clinicaltrials.gov) - P1/2 | N=17 | Recruiting | Sponsor: Ankit Mangla, MD | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • MTAP

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 | Trial primary completion date: May 2032 ➔ Aug 2028

Monotherapy • Trial primary completion date • Oncology • Solid Tumor • MTAP

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 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Oncology • Solid Tumor • MTAP

MountainTAP-29: A Study to Compare the Combination of Navlimetostat (BMS-986504) With Pembrolizumab and Chemotherapy Versus Placebo Plus Pembrolizumab and Chemotherapy in First-line Metastatic Non-small Cell Lung Cancer Participants With Homozygous MTAP Deletion (clinicaltrials.gov) - P2/3 | N=590 | Sponsor: Bristol-Myers Squibb | Phase classification: P=N/A ➔ P2/3

Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

CA240-0008: [14C]-BMS986504 Mass Balance Study in Patients with Advanced Solid Tumors with Homozygous MTAP Deletion (clinicaltrialsregister.eu) - P1 | N=16 | Recruiting | Sponsor: Bristol-Myers Squibb Services Unlimited Company

New P1 trial • Oncology • Solid Tumor

Safety and Efficacy of BMS-986504 in Unresectable Malignant Peripheral Nerve Sheath Tumor (clinicaltrials.gov) - P1/2 | N=17 | Not yet recruiting | Sponsor: Ankit Mangla, MD | Initiation date: Apr 2026 ➔ Aug 2026

Trial initiation date • Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • MTAP

A Study to Evaluate the Mass Balance, Metabolism, Elimination, and Drug Levels of [14C]-BMS-986504 (MRTX1719) in Participants With Advanced Solid Tumors With Homozygous Methylthioadenosine Phosphorylase Deletion (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Apr 2026 ➔ Oct 2027 | Trial primary completion date: Apr 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • MTAP

BMS-986504 in patients (pts) with advanced solid tumors with homozygous MTAP deletion (MTAP-del): Exploratory pharmacodynamic (PD) and biomarker analyses from CA240-0007. (ASCO 2026) - P1 | "BMS-986504 demonstrated robust dose-dependent PD effects in pts with advanced solid tumors in plasma SDMA and proteomic analyses. Downregulation of PRMT5-regulated pathways was observed with BMS-986504 treatment. Response was seen regardless of EGFR, KRAS, and TP53 alterations in NSCLC or PDAC, and DDR gene alterations were associated with improved response."

Biomarker • Clinical • Metastases • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CHEK2 • EGFR • FANCD2 • KRAS • MSH2 • MTAP • PRMT5 • SMARCA4 • STK11 • TP53 • XRCC4

A Study Comparing Navlimetostat (BMS-986504) in Combination With Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine in Participants With Untreated Metastatic Pancreatic Ductal Adenocarcinoma With Homozygous MTAP Deletion (MountainTAP-30) (clinicaltrials.gov) - P2/3 | N=470 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • MTAP

SELECTmeso A Trial for Patients With Relapsed Malignant Mesothelioma SELECTmeso1 A Trial of BMS-986504 in Patients With MTAP-deficient Relapsed Mesothelioma (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: University of Southampton

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

OncoKBTM, MSK's precision oncology knowledge base: 2024 updates (AACR 2025) - "OncoKB promoted BRAF fusions to Level 1 following inclusion as patient eligibility criteria in the FDA drug label for tovorafenib (low-grade glioma). Additionally, OncoKB included KRAS G12C in colorectal cancer and IDH1 mutations in myelodysplastic syndromes as Level 1 following FDA approval of adagrasib + cetuximab and ivosidenib, respectively...Lastly, novel biomarkers including FBXW7 and PPP2R1A alterations (endometrial and ovarian cancer), SMARCA4 mutations (non-small cell lung cancer and esophageal adenocarcinoma) and MTAP deletions (all solid tumors) were included in OncoKB based on compelling preclinical and emerging clinical evidence in association with lunresertib + camonsertib, PRT3789, and AMG193 and MRTX1719, respectively...OncoKB also implemented major software updates to support data integration into the EPIC platform. Future OncoKB efforts are focused on whole genome/exome curation, inclusion of biomarkers for non-NGS-based precision oncology therapies,..."

Tumor mutational burden • Brain Cancer • CNS Tumor • Colorectal Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Glioma • Hematological Malignancies • Lung Cancer • Microsatellite Instability • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Intestinal Carcinoma • Solid Tumor • BRAF • FBXW7 • IDH1 • KRAS • MSI • MTAP • POLD1 • PPP2R1A • SMARCA4 • TMB

A Phase 1 Study of Navlimetostat Tablet Formulations (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

Ph1/2 Trial Of Navlimetostat With Pumitamig In MTAP-Deficient Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=17 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • MTAP • NTRK • ROS1

BMS-986504 in Combination With Pemetrexed for the Treatment of Metastatic Solid Tumors With MTAP Deletion (clinicaltrials.gov) - P1/2 | N=72 | Not yet recruiting | Sponsor: Northwestern University

New P1/2 trial • Pan tumor • Biliary Cancer • Colon Cancer • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MTAP

A Study of BMS-986504 With Standard-of-Care Therapy for People With Solid Tumor Cancer (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P1 trial • Pan tumor • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • Urothelial Cancer • HER-2 • MTAP • PD-L1

A Study Comparing BMS-986504 in Combination With Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine in Participants With Untreated Metastatic Pancreatic Ductal Adenocarcinoma With Homozygous MTAP Deletion (MountainTAP-30) (clinicaltrials.gov) - P2/3 | N=470 | Recruiting | Sponsor: Bristol-Myers Squibb

Trial initiation date • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • MTAP