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

NCT07594626 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: NU 25MH07NCI-2026-03369STU00225627P30CA060553
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• Dose limiting toxicity

  Will be summarized descriptively by frequency and grade using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

  Up to 21 days

• Incidence of treatment-emergent adverse events (AEs)

  Will be summarized descriptively by frequency and grade using the NCI CTCAE v 5.0. Will be tabulated by system organ class and preferred term.

  Up to 30 days after last dose of study treatment

• Incidence of serious AEs

  Will be summarized descriptively by frequency and grade using the NCI CTCAE v 5.0.

  Up to 30 days after last dose of study treatment

• Incidence of grade 3 or greater adverse events

  Will be summarized descriptively by frequency and grade using the NCI CTCAE v 5.0.

  Up to 30 days after last dose of study treatment

• Number of patients who discontinue treatment due to toxicity

  Up to 30 days after last dose of study treatment

Secondary Outcomes (2)

• Objective response rate

  From baseline until disease progression, initiation of subsequent anti-cancer therapy, or completes study participation, whichever occurs first, assessed up to 12 months

• Duration of response (DOR)

  From the day when CR or PR is first observed until the earlier of the day of first documented disease progression or death from any cause, assessed up to 12 months

Study Arms (1)

Treatment (BMS-986504, pemetrexed)

EXPERIMENTAL

Patients receive BMS-986504 PO QD on days 1-21 and pemetrexed IV over 10 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and CT throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Pemetrexed; Drug: PRMT5 Inhibitor BMS-986504

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (BMS-986504, pemetrexed)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (BMS-986504, pemetrexed)

Pemetrexed DRUG

Given IV

Also known as: MTA, Multitargeted Antifolate, Pemfexy

Treatment (BMS-986504, pemetrexed)

PRMT5 Inhibitor BMS-986504 DRUG

Given PO

Also known as: BMS 986504, BMS-986504, BMS986504, MRTX 1719, MRTX-1719, MRTX1719, MTA-cooperative PRMT5 Inhibitor BMS-986504, MTA-cooperative PRMT5 Inhibitor MRTX1719, PRMT5-MTA Complex Inhibitor MRTX1719, PRMT5-MTA Inhibitor MRTX1719

Treatment (BMS-986504, pemetrexed)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Esophageal Neoplasms; Gastrointestinal Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms

Interventions

Specimen Handling; Pemetrexed

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Devalingam Mahalingam, MD, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

3126951301; cancer@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: May 19, 2026
• Study Start (Estimated): December 9, 2027
• Primary Completion (Estimated): December 9, 2030
• Study Completion (Estimated): December 9, 2030
• Last Updated: May 19, 2026

Record last verified: 2026-05

Locations

US (1)