Recruiting

Phase 1

Phase 2

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

Sponsor:

Northwestern University

Code:

NCT07594626

Conditions

Metastatic Biliary Tract Carcinoma

Metastatic Colon Carcinoma

Metastatic Esophageal Carcinoma

Metastatic Malignant Digestive System Neoplasm

Metastatic Malignant Solid Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Pemetrexed

PRMT5 Inhibitor BMS-986504

Study Details

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

Study ID

NCT07594626

Start date

Aug 21, 2026

Status verified date

Aug, 2026

Completion date

Dec 9, 2030

Anticipated

Primary completion date

Dec 9, 2030

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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:

Has not undergone a hysterectomy or bilateral oophorectomy
Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
POCBP are not permitted to use hormonal contraceptive methods alone as a highly effective method of contraception and must use an additional non-hormonal highly effective method of contraception. POCBP must agree to use a combination of a hormonal and a non-hormonal contraceptive method or a non-hormonal method alone that is highly effective (with a failure rate of < 1% per year) during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer
POCBP participants must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period
Male (as assigned at birth) participants will be required to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with POCBP, even if the participant has undergone a successful vasectomy or if the partner is pregnant or breastfeeding. Male (as assigned at birth) participants should continue to use a condom during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer
POCBP partners of male (as assigned at birth) participants should be advised to use a highly effective method of contraception during the intervention period and for at least 6 months after the last dose of study intervention for the male participant, or according to approved local product label requirements for pemetrexed, whichever is longer
Male (as assigned at birth) participants with a pregnant or breastfeeding partner must agree to remain abstinent from sexual activity or use a male condom during any sexual activity (eg, vaginal, anal, oral), even if the participant has undergone a successful vasectomy, during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer
Male (as assigned at birth) participants must refrain from donating sperm during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer
Breastfeeding partners of male (as assigned at birth) participants should be advised to consult their health care provider about using appropriate highly effective contraception during the time the male participant is required to use condoms
POCBP must have a negative pregnancy test prior to registration on study
The ability to interrupt nonsteroidal antiinflammatory drugs (NSAIDS) or aspirin at higher dose (> 1.3 g daily) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed

Exclusion Criteria:

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

NOTE: The following drug interaction databases and other literature can be utilized to determine the CYP3A4/P-gp inhibitors and inducers
Note: Please consult with the manufacturer for any uncertainties regarding potential CYP3A4 and P-gp modulators
Patients with inability to comply with restrictions and prohibited treatments
Patients taking any botanical preparation (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study within 4 weeks prior to treatment. The concurrent use of any botanical preparation is not permitted while on study
Patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration. Please note this lab is not a requirement for eligibility, however, if it has been completed previously as part of the patient's health care, it should be documented for eligibility
Patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Please note this lab is not a requirement for eligibility; however if it has been completed previously as part of the patient's health care, it should be documented for eligibility
Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with a known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Please note this lab is not a requirement for eligibility; however if it has been completed previously as part of the patient's health care, it should be documented for eligibility
Patients who take live/attenuated vaccine received within 30 days of first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction
Patient has not received the final dose of any of the following treatments/ procedures with the specified minimum intervals before first dose of study drug:

Surgery with general anesthesia - within 7 days of first dose of study drug
Surgery with local anesthesia - with 3 days of first dose of study drug

Study Design

Enrollment

72 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (BMS-986504, pemetrexed)

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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT

Pemetrexed

Given IV

PRMT5 Inhibitor BMS-986504

Given PO

Primary outcome measure

Dose limiting toxicity [ Time Frame: Up to 21 days ]
Incidence of treatment-emergent adverse events (AEs) [ Time Frame: Up to 30 days after last dose of study treatment ]
Incidence of serious AEs [ Time Frame: Up to 30 days after last dose of study treatment ]
Incidence of grade 3 or greater adverse events [ Time Frame: Up to 30 days after last dose of study treatment ]
Number of patients who discontinue treatment due to toxicity [ Time Frame: Up to 30 days after last dose of study treatment ]

Central Contacts and Locations

Central contacts

Study Coordinator

3126951301 cancer@northwestern.edu

Locations

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Devalingam Mahalingam, MD, PhD

210-413-1723 mahalingam@northwestern.edu

Principal Investigator:

Devalingam Mahalingam, MD, PhD

More Information

Sponsor

Northwestern University

Last update posted

Aug 25, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Northwestern University on 2026-08-25.