BMS‐986504 / BMS - LARVOL DELTA

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 | "Funded by Bristol Myers Squibb Clinical Trial Registration Number: NCT07076121 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P2/3 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • MTAP

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

PRIME: Clinical Trial to investigate the feasibility, safety, and tolerability of BMS-986504 in patients with recurrent MTAP-deleted Glioblastoma (ANZCTR) - P2 | N=10 | Not yet recruiting | Sponsor: Peter MacCallum Cancer Centre

New P2 trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT • MTAP

CA240-0009: A randomized, phase II study of BMS-986504 in patients with pretreated advanced or metastatic NSCLC with homozygous MTAP deletion (ESMO 2025) - P2 | "Secondary endpoints include disease control rate, clinical benefit rate, duration of response, progression-free survival, time to objective response, overall survival, safety, and health-related quality of life. The study is currently recruiting globally and will enroll approximately 130 patients."

Clinical • IO biomarker • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MAT2A • MTAP

­A phase 0/1 study of PRMT5 inhibitor BMS-986504 in recurrent glioblastoma participants with MTAP deleted tumors. (EANO 2025) - P1 | "This study will report, for the first time, unbound drug concentrations of a PRMT5-targeted inhibitor in gadolinium-nonenhancing tumor tissue from recurrent GBM patients, as well as associated on-target drug effects. This hybrid Phase 0/1 study is an important first-step to evaluate the use of PRMT5-inhibition to exploit synthetic lethality in MTAP-deleted GBM."

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

CA240-0007: BMS-986504 With Anti-PD-1 or Chemotherapy as Treatment for Advanced Solid Tumors With Homozygous MTAP Deletion (IASLC-WCLC 2025) - P1 | "Exclusion criteria specific to the PDAC substudy include a history of select lung diseases, connective tissue disorders, peripheral artery disease, chronic leukemias, or the ongoing need for warfarin or for a treatment known to inhibit or induce cytochrome P450 3A4 or 2C8 that cannot be switched to an alternative treatment prior to study entry. Further substudies with BMS-986504 combination regimens are planned. The combination substudies are currently recruiting, and approximately 155 patients will be enrolled across all substudies."

Metastases • CNS Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Peripheral Arterial Disease • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases • Rheumatology • Solid Tumor • MAT2A • MTAP

MTAPloss Is Frequent and Potentially Targetable With PRMT5 Inhibitors in Oncogene-Driven NSCL (IASLC-WCLC 2025) - "CRISPR-engineered MTAP knockout in EGFR + (HCC827) and ALK + (DFCI76) cell lines did not alter sensitivity to respective TKIs, with IC50 values of 0.01 μM for osimertinib (HCC827sgMTAP) and 0.01 μM for alectinib and lorlatinib (DFCI76sgMTAP), all comparable to parental controls. MRTX1719 monotherapy showed IC50 <0.5 μM in 5/7 EGFR + MTAP -deleted models, and <0.16 μM in all 5 ALK + MTAP -deleted lines...Preclinical data suggest that oncogene-driven tumors with MTAP loss are sensitive to single agent PRMT5 inhibitors and that combination TKI and PRMT5 inhibitors may have additive or synergistic antitumor activity. These findings support clinical testing of combined TKI and PRMT5 inhibitors in oncogene-driven MTAP deleted NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ALK • BRAF • CDKN2A • EGFR • HER-2 • KRAS • MTAP • ROS1

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

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 | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

MountainTAP-29: A Study to Compare the Combination of 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 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BMS-986504 demonstrates durable responses in MTAP-deleted NSCLC, including EGFR and ALK-positive tumors (Medical Xpress) - "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."

P1 data • Non Small Cell Lung Cancer

MountainTAP-29: A Study to Compare the Combination of 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 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

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

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 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

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

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

New P1 trial • Solid Tumor

Combination of the MTA-Cooperative PRMT5 Inhibitor BMS-986504 and KRAS Inhibitors is an Effective Treatment Strategy for MTAP-Deleted KRAS-Mutant Pancreatic Cancer. (PubMed, Cancer Res) - "While PRMT5 and KRAS regulated distinct transcriptomes, they converged on pathways governing cancer cell growth and expression of PDAC-essential genes. These findings provide rationale for combined inhibition of PRMT5 and KRAS in MTAP-deleted/KRAS-mutant PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • 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

Bristol Myers Squibb to Present Data at ASCO 2025 Highlighting Differentiated Research Platform of Oncology Treatments and Innovative Research Pipeline (Businesswire) - "Bristol Myers Squibb...announced the presentation of data across its oncology portfolio and pipeline at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting to be held May 30-June 3 in Chicago, Illinois. Data from more than 80 company-sponsored studies, investigator-sponsored studies, and collaborations showcase results spanning more than 20 cancer types."

Clinical data • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Myelodysplastic Syndrome • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Clinical Trial of BMS-986504 in Recurrent GBM Patients (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Nader Sanai | Trial completion date: Jun 2027 ➔ Sep 2027 | Trial primary completion date: Jun 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

A Study of BMS-986504 in Participants With Pre-treated Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) With Homozygous MTAP Deletion (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor