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

Official title

A Phase 2 Open-Label, Multi-Center Study of BMS-986504 as Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion

Overview

This is an open-label, multicenter Phase 2 study evaluating 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 BMS-986504 is given with other anti-cancer agents. The trial will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of BMS-986504 alone and in combination regimens.

Detailed description

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

Interventions

• Drug BMS-986504
  Specified dose on specified days
• Drug Daraxonrasib
  Specified dose on specified days
• Drug Nivolumab + Relatlimab FDC
  Specified dose on specified days
• Drug Temozolomide
  Specified dose on specified days
• Drug Pumitamig
  Specified dose on specified days
• Drug Pemetrexed
  Specified dose on specified days
• Drug Carboplatin
  Specified dose on specified days
• Drug Nab-paclitaxel
  Specified dose on specified days
• Drug Gemcitabine
  Specified dose on specified days
• Drug Paclitaxel
  Specified dose on specified days

Primary outcome measures

• Part 1: Number of participants who achieve Objective Response (OR) [Time frame: Up to approximately 2 years]
• Part 2: Number of participants with adverse events meeting protocol defined dose limiting toxicities (DLTs) criteria [Time frame: Up to approximately 2 years]
• Part 2: Number of participants with adverse events (AE) [Time frame: Up to approximately 2 years]
• Part 2: Number of participants with Serious AEs (SAEs) [Time frame: Up to approximately 2 years]
• Part 2: Number of participants with treatment related AEs [Time frame: Up to approximately 2 years]
• Part 2: Number of participants with treatment related SAEs [Time frame: Up to approximately 2 years]
• Part 2: Number of participants with AEs leading to study treatment discontinuation [Time frame: Up to approximately 2 years]
• Part 2: Number of participants with AEs leading to death [Time frame: Up to approximately 2 years]
• Part 2: Number of participants with laboratory abnormalities [Time frame: Up to approximately 2 years]

Secondary outcome measures (12)

• Part 1 and 2: Time to objective response (TTOR) [Time frame: Up to approximately 2 years]
• Part 1 and 2: Duration of response (DOR) [Time frame: Up to approximately 2 years]
• Part 1 and 2: Number of participants who achieve disease control (DC) [Time frame: Up to approximately 2 years]
• Part 1: Number of participants with adverse events (AE) [Time frame: Up to approximately 2 years]
• Part 1: Number of participants with Serious AEs (SAEs) [Time frame: Up to approximately 2 years]
• Part 1: Number of participants with treatment related AEs [Time frame: Up to approximately 2 years]
• Part 1: Number of participants with treatment related SAEs [Time frame: Up to approximately 2 years]
• Part 1: Number of participants with AEs leading to study treatment discontinuation [Time frame: Up to approximately 2 years]
• Part 1: Number of participants with AEs leading to death [Time frame: Up to approximately 2 years]
• Part 1: Number of participants with laboratory abnormalities [Time frame: Up to approximately 2 years]
• Part 2: Number of participants who achieve Objective Response (OR) [Time frame: Up to approximately 2 years]
• Part 1 and 2: Number of participants who achieved clinical benefit (CB) [Time frame: Up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Participant must have histologically confirmed diagnosis of advanced and/or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene 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.
• Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) must be ≤ 1.5 × ULN; subjects with liver metastasis or liver cancer must be ≤ 2 × ULN.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 16 centers

• Local Institution - 0096 — San Francisco
• Local Institution - 0182 — Aurora
• Local Institution - 0178 — Atlanta
• Johns Hopkins Hospital — Baltimore
• Local Institution - 0124 — Boston
• Local Institution - 0119 — Ann Arbor
• Local Institution - 0129 — Rochester
• Local Institution - 0174 — Rochester
• … and 8 more centers

China · 6 centers

• Local Institution - 0155 — Beijing
• Local Institution - 0185 — Chongqing
• Local Institution - 0184 — Guangzhou
• Local Institution - 0152 — Xinxiang
• Shanghai GoBroad Cancer Hospital China Pharmaceutical University — Shanghai
• Fudan University Shanghai Cancer Center — Shanghai

Germany · 6 centers

• Local Institution - 0081 — Mainz
• Local Institution - 0040 — Hamburg
• Local Institution - 0039 — Heidelberg
• Local Institution - 0061 — Leipzig
• Local Institution - 0049 — München
• Local Institution - 0047 — Würzburg

Italy · 5 centers

• Local Institution - 0073 — Siena
• Local Institution - 0123 — Bergamo
• Local Institution - 0034 — Milan
• Local Institution - 0050 — Naples
• Local Institution - 0082 — Perugia

France · 4 centers

• Local Institution - 0078 — Dijon
• Local Institution - 0075 — Pierre-Bénite
• Local Institution - 0116 — Villejuif
• Local Institution - 0074 — Paris

Spain · 4 centers

• Local Institution - 0068 — Barcelona
• Local Institution - 0071 — Hospitalet
• Local Institution - 0033 — Madrid
• Local Institution - 0069 — Seville

Canada · 3 centers

• Local Institution - 0051 — Vancouver
• Local Institution - 0021 — Toronto
• Local Institution - 0007 — Toronto

Ireland · 3 centers

• Local Institution - 0080 — Cork
• Local Institution - 0023 — Dublin
• Local Institution - 0146 — Dublin

South Korea · 3 centers

• Local Institution - 0004 — Seoul
• Local Institution - 0058 — Seoul
• Local Institution - 0052 — Seoul

Belgium · 2 centers

• Local Institution - 0148 — Brussels
• Local Institution - 0114 — Ghent

Hong Kong · 2 centers

• Local Institution - 0150 — Hksar
• Local Institution - 0063 — Shatin

Norway · 2 centers

• Local Institution - 0171 — Bergen
• Local Institution - 0022 — Oslo

Japan · 1 center

• National Cancer Center Hospital — Chuo-ku

Identifiers

NCT: NCT07492680 · CA240-0005 · 2025-524285-18 · U1111-1330-1428

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗