Phase 1b Trial of BMS-986504 in Combination With Olaparib in Patients With MTAP Loss

NCT07382544 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2025-1200NCI-2025-09342
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn about the safety and effects of BMS-986504 in combination with olaparib in patients with advanced solid tumors with MTAP loss.

Conditions

Advanced Cancer; Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (3)

Part A Dose Escalation: Treatment with BMS-986504 + Olaparib

EXPERIMENTAL

Study treatment will be administered on an outpatient basis

Drug: MRTX1719; Drug: Olaparib

Part B Pharmacodynamic Expansion Cohort 1: Treatment with BMS-986504 at C1D1 + Olaparib at C1D15

EXPERIMENTAL

Study treatment will be administered on an outpatient basis

Drug: MRTX1719; Drug: Olaparib

Part B Pharmacodynamic Expansion Cohort 2: Treatment with Olaparib at C1D1 + BMS-986504 at C1D15

EXPERIMENTAL

Study treatment will be administered on an outpatient basis

Drug: MRTX1719; Drug: Olaparib

Interventions

MRTX1719 DRUG

Given by mouth

Part A Dose Escalation: Treatment with BMS-986504 + Olaparib; Part B Pharmacodynamic Expansion Cohort 1: Treatment with BMS-986504 at C1D1 + Olaparib at C1D15; Part B Pharmacodynamic Expansion Cohort 2: Treatment with Olaparib at C1D1 + BMS-986504 at C1D15

Olaparib DRUG

Given by mouth

Also known as: Lynparza

Part A Dose Escalation: Treatment with BMS-986504 + Olaparib; Part B Pharmacodynamic Expansion Cohort 1: Treatment with BMS-986504 at C1D1 + Olaparib at C1D15; Part B Pharmacodynamic Expansion Cohort 2: Treatment with Olaparib at C1D1 + BMS-986504 at C1D15

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• All patients must have a histologically confirmed advanced or metastatic solid tumor that has been refractory to standard therapy or are not eligible for standard therapy and have no alternative curative-intent treatment options at the time of patient enrollment. For the dose escalation, any solid tumor is eligible, but enrollment will be enriched for CCA and pancreatic cancer. For the pharmacodynamic expansion, patients must have histologically confirmed advanced or metastatic CCA or pancreatic cancer.
• Homozygous deletion of MTAP as detected by Clinical Laboratory Improvement Amendmentscertified next-generation sequencing test or absence of MTAP protein as detected by CLIAcertified immunohistochemistry test.
• Patients in Part A must have archived tumor tissue available for retrospective analysis or agree to pre-treatment biopsy.
• Ability to understand and the willingness to sign a written informed consent document.
• Ability to comply with the study protocol, in the investigator's judgment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1).
• Life expectancy ≥3 months.
• Patients in the pharmacodynamic expansion must have measurable and biopsiable disease per the RECIST v1.1 (Appendix 2). Patients in the dose escalation can have evaluable or measurable disease.
• Patients must have adequate washout from prior therapy at the time of study treatment initiation: 3 weeks from any treatment specifically for systemic tumor control: 5 half-lives from small molecule targeted agents and ≥ 2 weeks from radiotherapy (except for patients with brain metastasis treatment with Gamma Knife; in these cases, \> 1 week is required). Palliative radiotherapy is permitted for a preexisting lesion, provided it does not interfere with the assessment of tumor target lesions (e.g., the lesion to be irradiated must not be a site of measurable disease).
• Patients must have recovered from toxicities of prior anticancer therapy (Grade ≤ 1 toxicity) except for alopecia and peripheral neuropathy.
• Adequate organ and marrow function as defined below within 28 days prior to study treatment initiation:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelets ≥ 100,000/mm3

You may not qualify if:

• Part B only: Prior treatment with a PRMT5 or methionine adenosyltransferase 2A inhibitor.
• Patients who have a known additional malignancy that is progressing or requires active treatment at time of study treatment initiation. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer.
• Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastases. Note: Patients with stable brain metastases (defined as asymptomatic or no requirement for high-dose or increasing dose of systemic corticosteroids and without imminent need of radiation therapy) are eligible (including those with untreated brain metastases). If applicable, patients must have completed brain radiation therapy and recovered adequately from any associated toxicity and/or complications prior to eligibility assessment.
• Concomitant use of strong cytochrome P450 (CYP)3A inhibitors or inducers are prohibited within 14 days or 5 half-lives, whichever is longer, prior to study treatment initiation and during the study treatment period. For a comprehensive list of CYP3A inhibitors/inducers, refer to: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactionstable-substrates-inhibitors-and-inducers.
• Any clinically significant comorbidities such as uncontrolled pulmonary disease, known impaired cardiac function or clinically significant cardiac disease (including but not limited to known left ventricular ejection fraction \< 50%, congenital long QT syndrome, corrected QT interval using Fridericia's formula ≥ 480 msec on screening electrocardiogram \[ECG\], unstable angina pectoris ≤ 3 months prior to study treatment initiation, and acute myocardial infarction ≤ 3 months prior to study treatment initiation), or any other condition that could compromise the patient's participation in the study.
• Treatment with a live, attenuated vaccine within 4 weeks prior to study treatment initiation.
• Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacille Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Non-live COVID vaccines will be allowed on study, but it is recommended to avoid their use during the first treatment cycle (from 3 days prior to Cycle 1 Day 1 through Cycle 2 Day 3).
• Concomitant use of medications known to be sensitive substrates of breast cancer resistance protein (including, but not limited to, rosuvastatin and sulfasalazine) or P-glycoprotein (P-gp; including, but not limited to, dabigatran etexilate, digoxin, fexofenadine).
• Patients who are pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 7 months after the last dose of study treatment.
• Any known psychiatric, substance abuse, or other disorder that would interfere with cooperation with the requirements of the study, in the opinion of the investigator.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs.
• Patients who have an active infection requiring intravenous (IV) antibiotics.
• Patients with any gastrointestinal disorder that would significantly alter the absorption of the study drugs (e.g., active ulcerative diseases, uncontrolled nausea, uncontrolled vomiting, uncontrolled diarrhea, malabsorption syndrome).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

olaparib

Study Officials

• Jordi Rodon Ahnert, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jordi Rodon Ahnert, MD, PHD

CONTACT

(713) 792-5603; jrodon@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: December 29, 2025
• First Posted: February 3, 2026
• Study Start: February 12, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): January 31, 2032
• Last Updated: February 25, 2026

Record last verified: 2026-02

Locations

US (1)