BMS-986504 in Combination With Pemetrexed for the Treatment of Metastatic Solid Tumors With MTAP Deletion

Starting soon · Phase 1/Phase 2

Conditions studied: Metastatic Biliary Tract Carcinoma, Metastatic Colon Carcinoma, Metastatic Esophageal Carcinoma, Metastatic Malignant Digestive System Neoplasm, Metastatic Malignant Solid Neoplasm, Metastatic Pancreatic Carcinoma, Stage IV Colon Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8

In brief

This phase Ib/II trial tests the safety and side effects of BMS-986504 in combination with pemetrexed and how well the combination works in treating patients with solid tumors with MTAP deletion and that has spread from where it first started (primary site) to other places in the body (metastatic). The MTAP gene helps cells recycle important parts needed to make deoxyribonucleic acid (DNA), which is needed for cell growth and function. MTAP deletion means that the MTAP gene is missing. BMS-986504, a PRMT5 inhibitor, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Giving BMS-986504 in combination with pemetrexed may be safe, tolerable, and/or effective in treating patients with metastatic solid tumors with MTAP deletion.

Key facts

Study ID

NCT07594626

Run by

Northwestern University

People needed

72

Starts

2027-12-09

Expected to finish

2030-12-09

Last updated by the study team

2026-05-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• COHORT A (INCLUDING SAFETY RUN IN, STAGE I AND STAGE II) AND COHORT B:
• Patients must have pathologically or cytologically confirmed metastatic solid tumor of gastrointestinal origin with MTAP deletion including pancreatic cancer, biliary cancer, esophageal cancer and colon cancer (Cohort A) or other metastatic solid malignancy with MTAP deletion (Cohort B) confirmed by validated next generation sequencing tissue techniques only
• NOTE: Both internal and external validated next generation sequencing (NGS) panels are acceptable
• Progressive disease (PD) after one previous standard of care line of treatment
• NOTE: symptoms from clinical evaluation for PD will be sufficient
• Patients must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, measured preferably by computed tomography (CT) scan
• Note: Tumor lesions in a previously irradiated area are not considered measurable unless they show unequivocal progression
• NOTE: There is no limit on previous treatment lines
• Patients who have received any neoadjuvant or systemic chemotherapy are eligible
• Note: treatment cannot have included prior pemetrexed unless in the case of non-small cell lung cancer (NSCLC) cancer type. Any prior intravesical therapy, or immunotherapy is allowed. At least 3 weeks (21 days) wash-out period from treatment since prior chemotherapy or radiation therapy or targeted agent is required
• Patients must be aged ≥ 18 years
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Absolute neutrophil count (ANC) ≥ 1,500/mcL (growth factor allowed and can be added at the discretion of the treating oncologist
• Growth factors are excluded from being used during the DLT observation period (cycle 1) unless they are being used to treat a grade 4 adverse event which will be counted as a DLT. If growth factors are being used for grade ≤ 3 toxicity, then patients will not be evaluable for DLT assessment
• Hemoglobin (Hgb) ≥ 8.5 g/dL (without the need for transfusion within the previous one week)
• Platelets (PLT) ≥ 100,000/mL (without the need for platelet transfusion within the previous one week)
• Total bilirubin ≤ 1.5 x Institutional upper limit of normal (ULN), except subjects with Gilbert's syndrome or liver metastases, who must have a baseline total bilirubin ≤ 3.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present
• Creatinine clearance ≥ 60 mL/min/1.73 m\^2 using the standard Cockcroft and Gault formula
• Patients must have the ability to comply with folic acid, vitamin B12 and steroids as directed by study team and as per standard of care for pemetrexed use
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
• Pemetrexed is known to be teratogenic. Reproductive toxicology studies with MRTX1719 have not been performed. The investigator or designee shall counsel patients of childbearing potential (POCBP) participants and male (as assigned at birth) participants who are sexually active with POCBP on the importance of pregnancy prevention, the implications of an unexpected pregnancy, and the potential of fetal toxicity occurring due to transmission of study intervention present in seminal fluid to a developing fetus, even if the participant has undergone a successful vasectomy or if the partner is pregnant. If needed, participants should be advised to seek advice about egg or sperm donation and cryopreservation of germ cells before treatment
• Patients of childbearing potential POCBP
• A POCBP is any patient with an egg-producing reproductive tract who meets the following criteria:

You may not qualify if…

• STAGE I AND II, COHORT A (INCLUDING SAFETY RUN IN) AND B:
• Patients who received prior pemetrexed containing chemotherapy (apart from NSCLC)
• Patients with prior treatment with a PRMT5 or MAT2A inhibitor therapy
• Patients with pre-existing clinically significant interstitial lung disease (ILD)
• Patients who have had chemotherapy or radiotherapy ≤ 21 days prior to planned treatment start date.
• Note: seven days or fewer of palliative radiotherapy for non-CNS disease, is permitted. No wash-out is required
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and neuropathy per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
• Patients who are receiving any other investigational agents or devices. Patients start of study treatment will be based on their discontinuation and recovery from clinically significant adverse events from their most recent therapy or intervention prior to study enrollment
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pemetrexed
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:
• Ongoing or active infection requiring systemic treatment
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification
• Note: To be eligible for this trial, patients should be class 2B or better
• Patients with presence of third space fluid which cannot be controlled by drainage
• Note: For patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. However, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy
• Patients who are not able to understand and voluntarily sign a written informed consent and is not willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures
• Patients who are pregnant or nursing
• Patients with history of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications
• Patients with Fridericia's formula-corrected QT interval (QTcF) prolongation > 480 msec, except for right bundle branch block, per the investigator's assessment
• Patients with ongoing need for a medication with a known risk of Torsade's de Pointes that cannot be switched to an alternative treatment prior to study entry
• Patients with ongoing need for a medication known as a strong inhibitor or strong inducer of cytochrome P450 3A4 (CYP3A4) and/or P-glycoprotein (P-gp) or a proton-pump inhibitor and potassium-competitive acid blockers that cannot be switched to an alternative treatment prior to study entry

Where it is running

• Northwestern University — Chicago, Illinois, United States

Full record on ClinicalTrials.gov

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