A Study of Navlimetostat (BMS-986504) Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5)

Bristol-Myers Squibb (BMS)

Status and phase: Enrolling; Phase 2

Conditions: Solid Tumors

Treatments: Drug: Carboplatin; Drug: Temozolomide; Drug: Navlimetostat; Drug: Nab-paclitaxel; Drug: Daraxonrasib; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Cisplatin; Drug: Pemetrexed; Drug: Pumitamig

Study type: Interventional

Funder types: Industry

Identifiers

NCT07492680

U1111-1330-1428 (Other Identifier)

CA240-0005

2025

2025-524285-18 (Other Identifier)

Details and patient eligibility

About

This is an open-label, multicenter Phase 2 study evaluating Navlimetostat (BMS-986504) in participants with advanced and/or metastatic solid tumors that have MTAP deletion. The study includes a monotherapy component and a combination component in which Navlimetostat (BMS-986504) is given with other anti-cancer agents. The trial will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of Navlimetostat (BMS-986504) alone and in combination regimens.

Full description

Part 1 will include parallel enrolment of tumor-specific dose-expansion cohorts evaluating Navlimetostat (BMS-986504) as monotherapy. Part 2 will include dose-escalation cohorts in which Navlimetostat (BMS-986504) is given in combination with other anticancer agents. Additional cohorts may be added based on emerging data.

Enrollment: 254 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant must have histologically confirmed diagnosis of advanced and/or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene or MTAP loss detected in tumor tissue.
• Depending on the cohort enrolled, participants must have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment (there must be no available treatment with curative intent or participant is ineligible or declines treatment) or be treatment-naïve with no prior systemic anticancer therapy for their unresectable or metastatic disease.
• Participant must have presence of at least one measurable tumor lesion per RECIST v1.1 or mRECIST at baseline and Radiologic assessment in neuro-oncology (RANO)2.0 as applicable at baseline.
• Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) must be ≤ 1.5 × ULN; or ≤ 2 x ULN in subjects with liver metastasis or liver cancer.
• Participant must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion criteria

• Participants must not have prior treatment with a PRMT5 or Methionine adenosyl transferase 2A (MAT2A) inhibitor.
• Participants must not have active brain metastases or carcinomatous meningitis. Participants are eligible if brain metastases are adequately treated, and participants are neurologically stable for at least 2 weeks prior to enrollment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
• Participants must not have history of gastrointestinal disease or other gastrointestinal conditions within 6 months prior to enrollment (including uncontrolled nausea, vomiting, malabsorption syndrome or non-gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess) likely to alter absorption of study treatment or result in inability to swallow oral medications.
• Participants must not have inadequate organ function, as determined by laboratory testing within the screening period.
• Participants must not have active viral HBV or HCV hepatitis.
• Other protocol defined inclusion/exclusion criteria applies.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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254 participants in 7 patient groups

Part 1a

Experimental group

Description:

Navlimetostat (BMS-986504)

Treatment:

Drug: Navlimetostat

Part 1b

Experimental group

Description:

Navlimetostat (BMS-986504)

Treatment:

Drug: Navlimetostat

Part 2: Cohort 1

Experimental group

Description:

Navlimetostat (BMS-986504) + Pumitamig + Chemotherapy

Treatment:

Drug: Pumitamig

Drug: Pemetrexed

Drug: Cisplatin

Drug: Paclitaxel

Drug: Nab-paclitaxel

Drug: Navlimetostat

Drug: Carboplatin

Part 2: Cohort 2a

Experimental group

Description:

Navlimetostat (BMS-986504) + Daraxonrasib

Treatment:

Drug: Daraxonrasib

Drug: Navlimetostat

Part 2: Cohort 2b

Experimental group

Description:

Navlimetostat (BMS-986504) + Daraxonrasib

Treatment:

Drug: Daraxonrasib

Drug: Navlimetostat

Part 2: Cohort 2c

Experimental group

Description:

Navlimetostat (BMS-986504) + Daraxonrasib + Chemotherapy

Treatment:

Drug: Gemcitabine

Drug: Daraxonrasib

Drug: Nab-paclitaxel

Drug: Navlimetostat

Part 2: Cohort 4

Experimental group

Description:

Navlimetostat (BMS-986504) + Temozolomide + Radiotherapy

Treatment:

Drug: Navlimetostat

Drug: Temozolomide