Sponsor: Bristol-Myers Squibb (industry)
Phase: 2/3
Start date: July 21, 2025
Planned enrollment: 470
BMS-986504 (also known as MRTX1719) is an oral, selective MTA‑cooperative PRMT5 inhibitor being developed for tumors with homozygous MTAP deletion (MTAP‑del), a genomic alteration present in roughly 10% of cancers. The agent originated at Mirati Therapeutics as MRTX1719 and is now being advanced by Bristol Myers Squibb; multiple medicinal chemistry reviews explicitly note the synonymy BMS‑986504 = MRTX1719. Early clinical experience has shown antitumor activity across MTAP‑del solid tumors, and dedicated phase 2/3 trials in NSCLC are underway. (pubmed.ncbi.nlm.nih.gov)
Key translational evidence from a peer‑reviewed study (Cancer Discovery, 2023): - >70‑fold selectivity for MTAP‑del vs MTAP‑WT cells; dose‑dependent SDMA inhibition in MTAP‑del tumors with minimal effects in hematopoietic cells. (aacrjournals.org)
Notes: Where conference or company communications are cited, results should be considered preliminary until peer‑reviewed full manuscripts are available.
Last updated: Oct 2025
Goal: Evaluate whether adding BMS-986504, a selective MTA-cooperative PRMT5 inhibitor, to standard first-line nab-paclitaxel/gemcitabine improves outcomes versus placebo plus nab-paclitaxel/gemcitabine in untreated metastatic PDAC with homozygous MTAP deletion or demonstrable MTAP loss.
Patients: Adults with histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma harboring homozygous MTAP deletion or MTAP loss, with at least one measurable lesion by RECIST v1.1, and no prior systemic therapy for metastatic disease. One induction cycle of nab-paclitaxel/gemcitabine before randomization is allowed if no progression or intolerable toxicity occurred. Key exclusions include active concurrent malignancy requiring treatment within 2 years and other protocol-defined criteria.
Design: Randomized, placebo-controlled, multi-arm Phase 2/3 study with parallel assignment comparing BMS-986504 plus nab-paclitaxel/gemcitabine versus placebo plus nab-paclitaxel/gemcitabine. Approximately 470 participants will be enrolled, with efficacy assessed per RECIST v1.1 and time-to-event endpoints followed up to three years post last randomization.
Treatments: Experimental arms receive BMS-986504 in combination with nab-paclitaxel and gemcitabine; control arms receive placebo with nab-paclitaxel and gemcitabine. BMS-986504 (formerly MRTX1719) is an investigational, selective MTA-cooperative PRMT5 inhibitor that targets the PRMT5–MTA complex, exploiting synthetic lethality in MTAP-deleted tumors by disrupting essential arginine methylation. In a prior Phase 1/2 study across MTAP-deleted solid tumors, BMS-986504 showed an objective response rate of about 23% in heavily pretreated patients and was generally well tolerated. Nab-paclitaxel plus gemcitabine is a standard first-line regimen in metastatic PDAC.
Outcomes: Co-primary endpoints are progression-free survival by RECIST v1.1 and overall survival. Key secondary endpoints include objective response rate, duration of response, time to objective response, disease control rate, and a secondary analysis of PFS by RECIST v1.1. Assessments are planned for up to three years after the last participant is randomized.
Burden on patient: Moderate. The backbone chemotherapy and imaging schedule will resemble standard first-line PDAC care with RECIST-based scans at regular intervals, but participation adds required screening for MTAP status and protocolized assessments. As an oral targeted agent, BMS-986504 is unlikely to add infusion time beyond chemotherapy; however, investigational therapy typically entails more frequent clinic visits early in treatment, additional laboratory monitoring for safety, and potential on-study tumor tissue confirmation. No intensive pharmacokinetic sampling typical of Phase 1 is expected, but Phase 2/3 safety labs and imaging may increase visit frequency compared with routine practice. Travel burden aligns with chemotherapy infusion schedules, with added visits for study-specific evaluations.
Last updated: Nov 2025
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma (PDAC).
* Evidence of homozygous methylthioadenosine phosphorylase (MTAP) deletion or MTAP loss detected in tumor tissue.
* Metastatic disease with at least 1 measurable lesion as per Response Evaluation Criteria in Solid Tumors version v1.1 (RECIST v1.1).
* Participants must not have received any systemic anticancer treatments in the metastatic setting.
* If clinically indicated and as per investigator discretion, participants may receive up to 1 cycle of Nab-paclitaxel/Gemcitabine (nab-p/gem) in the metastatic setting and must have not progressed or required discontinuation due to intolerable toxicity.
* Initial cycle of nab-p/gem administered in the metastatic setting must have been completed prior to randomization.
Exclusion Criteria:
* Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to screening.
* Other protocol-defined Inclusion/Exclusion criteria apply.
Buenos Aires, 1431, Argentina
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Córdoba, 5000, Argentina
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Ciudad Autónoma de Buenos Aires, Buenos Aires, 1280, Argentina
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Ciudad Autónoma de Buenos Aires, Buenos Aires, C1426ANZ, Argentina
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San Miguel de Tucumán, Tucumán Province, 4000, Argentina
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St Leonards, New South Wales, 2065, Australia
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Lund, Skåne Län [se-12], 22185, Sweden
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Bellinzona, Canton Ticino, 6500, Switzerland
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Luoyang, Henan, 471003, China
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Jining, Shandong, 272029, China
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No email / No phone
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Bogotá, 110411, Colombia
No email / No phone
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No email / No phone
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No email / No phone
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Montería, Departamento de Córdoba, 230002, Colombia
No email / No phone
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Prague, 12808, Czechia
No email / No phone
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Olomouc, Olomouc Region, 779 00, Czechia
No email / No phone
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Prague, Praha 5, 150 06, Czechia
No email / No phone
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Aalborg, North Denmark, 9000, Denmark
No email / No phone
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Lyon, Auvergne-Rhône-Alpes, 69003, France
No email / No phone
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Montpellier, Hérault, 34298, France
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Shatin, NT, Hong Kong
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Kochi, Kerala, 682041, India
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New Delhi, National Capital Territory of Delhi, 110029, India
No email / No phone
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Bhubaneswar, Odisha, 751003, India
No email / No phone
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Hyderabad, Telangana, 500033, India
No email / No phone
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Hyderabad, Telangana, 500032, India
No email / No phone
Status: Not yet recruiting
Varanasi, Uttar Pradesh, 221005, India
No email / No phone
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Kolkata, West Bengal, 700094, India
No email / No phone
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Petah Tikva, 4941492, Israel
No email / No phone
Status: Not yet recruiting
Ramat Gan, Central District, 5265601, Israel
No email / No phone
Status: Not yet recruiting
Ẕerifin, Central District, 70300, Israel
No email / No phone
Status: Not yet recruiting
Jerusalem, Jerusalem, 9112001, Israel
No email / No phone
Status: Not yet recruiting
Afula, Northern District, 1834111, Israel
No email / No phone
Status: Not yet recruiting
Tel Aviv, Tell Abīb, 6423906, Israel
No email / No phone
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Osaka, 541-8567, Japan
No email / No phone
Status: Not yet recruiting
Nagoya, Aichi-ken, 464-8681, Japan
No email / No phone
Status: Not yet recruiting
Sapporo, Hokkaido, 060-8543, Japan
No email / No phone
Status: Not yet recruiting
Yokohama, Kanagawa, 2418515, Japan
No email / No phone
Status: Not yet recruiting
Lembah Pantai, Kuala Lumpur, 59100, Malaysia
No email / No phone
Status: Not yet recruiting
Kuala Lumpur, Kuala Lumpur, 50586, Malaysia
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Kuching, Sarawak, 93586, Malaysia
No email / No phone
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Puebla City, 72424, Mexico
No email / No phone
Status: Not yet recruiting
Querétaro, 76000, Mexico
No email / No phone
Status: Not yet recruiting
Zapopan, Jalisco, 45050, Mexico
No email / No phone
Status: Not yet recruiting
Mexico City, Mexico City, 03100, Mexico
No email / No phone
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Cuauhtémoc, Ciudad de México, Mexico City, 06100, Mexico
No email / No phone
Status: Not yet recruiting
Monterrey, Nuevo León, 64460, Mexico
No email / No phone
Status: Not yet recruiting
Oaxaca City, Oaxaca, 68020, Mexico
No email / No phone
Status: Not yet recruiting
Mérida, Yucatán, 97070, Mexico
No email / No phone
Status: Not yet recruiting
Maastricht, Limburg, 6229 HX, Netherlands
No email / No phone
Status: Not yet recruiting
Breda, North Brabant, 4818 CK, Netherlands
No email / No phone
Status: Not yet recruiting
Rotterdam, South Holland, 3015 GD, Netherlands
No email / No phone
Status: Not yet recruiting
Leiden, South Holland, 2333 ZA, Netherlands
No email / No phone
Status: Not yet recruiting
Warsaw, 02-781, Poland
No email / No phone
Status: Not yet recruiting
Gdask, Pomeranian Voivodeship, 80-952, Poland
No email / No phone
Status: Not yet recruiting
Singapore, 308433, Singapore
No email / No phone
Status: Not yet recruiting
Singapore, 329563, Singapore
No email / No phone
Status: Not yet recruiting
Banská Bystrica, 97517, Slovakia
No email / No phone
Status: Not yet recruiting
Bratislava, 83101, Slovakia
No email / No phone
Status: Not yet recruiting
Košice, Košice Region, 041 91, Slovakia
No email / No phone
Status: Not yet recruiting
Trenčín, Trenčín Region, 911 01, Slovakia
No email / No phone
Status: Not yet recruiting
Soweto, Gauteng, 2013, South Africa
No email / No phone
Status: Not yet recruiting
Pretoria, Gauteng, 0001, South Africa
No email / No phone
Status: Not yet recruiting
Johannesburg, Gauteng, 2193, South Africa
No email / No phone
Status: Not yet recruiting
Cape Town, Western Cape, 7937, South Africa
No email / No phone
Status: Not yet recruiting
Adana, 01250, Turkey (Türkiye)
No email / No phone
Status: Not yet recruiting
Istanbul, 34899, Turkey (Türkiye)
No email / No phone
Status: Not yet recruiting
Ankara, 06230, Turkey (Türkiye)
No email / No phone
Status: Not yet recruiting
Ankara, 06560, Turkey (Türkiye)
No email / No phone
Status: Not yet recruiting
Stanbul, Istanbul, 34214, Turkey (Türkiye)
No email / No phone
Status: Not yet recruiting
Phoenix, Arizona, 85054, United States
No email / No phone
Status: Not yet recruiting
Tucson, Arizona, 85724, United States
No email / No phone
Status: Not yet recruiting
San Francisco, California, 94115, United States
No email / No phone
Status: Not yet recruiting
Jacksonville, Florida, 32224, United States
No email / No phone
Status: Not yet recruiting
Jacksonville, Florida, 32207, United States
No email / No phone
Status: Not yet recruiting
Atlanta, Georgia, 30322, United States
No email / No phone
Status: Not yet recruiting
Chicago, Illinois, 60637, United States
No email / No phone
Status: Not yet recruiting
Westwood, Kansas, 66205, United States
No email / No phone
Status: Not yet recruiting
Louisville, Kentucky, 40202, United States
No email / No phone
Status: Not yet recruiting
Baltimore, Maryland, 21287, United States
No email / No phone
Status: Not yet recruiting
Baltimore, Maryland, 21201, United States
No email / No phone
Status: Not yet recruiting
Boston, Massachusetts, 02215, United States
No email / No phone
Status: Not yet recruiting
Rochester, Minnesota, 55905, United States
No email / No phone
Status: Not yet recruiting
New York, New York, 10029, United States
No email / No phone
Status: Not yet recruiting
New York, New York, 10065, United States
No email / No phone
Status: Not yet recruiting
Columbus, Ohio, 43210, United States
No email / No phone
Status: Not yet recruiting
Portland, Oregon, 97239, United States
No email / No phone
Status: Not yet recruiting
Philadelphia, Pennsylvania, 19107, United States
No email / No phone
Status: Not yet recruiting
Pittsburgh, Pennsylvania, 15232, United States
No email / No phone
Status: Not yet recruiting
Lancaster, Pennsylvania, 17601, United States
No email / No phone
Status: Not yet recruiting
Pittsburgh, Pennsylvania, 15212, United States
No email / No phone
Status: Not yet recruiting
Temple, Texas, 76508, United States
No email / No phone
Status: Not yet recruiting
Fort Worth, Texas, 76177, United States
No email / No phone
Status: Not yet recruiting
Salt Lake City, Utah, 84111, United States
No email / No phone
Status: Not yet recruiting
Norfolk, Virginia, 23502, United States
No email / No phone
Status: Not yet recruiting
Seattle, Washington, 98101, United States
No email / No phone
Status: Not yet recruiting
Milwaukee, Wisconsin, 53226, United States
No email / No phone
Status: Not yet recruiting
Viña del Mar, Valparaiso, 2520598, Chile
No email / No phone
Status: Withdrawn
Fuzhou, Fujian, 350014, China
No email / No phone
Status: Withdrawn
Wuhan, Hubei, 430079, China
No email / No phone
Status: Withdrawn
Shanghai Shi, Shanghai Municipality, 200032, China
No email / No phone
Status: Withdrawn
Shanghai, Shanghai Municipality, 200032, China
No email / No phone
Status: Withdrawn
Rionegro, Antioquia, 054047, Colombia
No email / No phone
Status: Withdrawn
Pereira, Risaralda Department, 660001, Colombia
No email / No phone
Status: Withdrawn
Aarhus, Central Jutland, 8200, Denmark
No email / No phone
Status: Withdrawn
Mexico City, 14210, Mexico
No email / No phone
Status: Withdrawn
Tampa, Florida, 33612, United States
No email / No phone
Status: Withdrawn