A Study to Compare the Combination of BMS-986504 With Pembrolizumab and Chemotherapy Versus Placebo Plus Pembrolizumab and Chemotherapy in First-line Metastatic Non-small Cell Lung Cancer Participants With Homozygous MTAP Deletion (MountainTAP-29)

Bristol-Myers Squibb (BMS)

Status and phase: Begins enrollment in 2 months; Phase 3; Phase 2

Conditions: Metastatic Non-small Cell Lung Cancer With MTAP Deletion

Treatments: Drug: Cisplatin; Drug: Paclitaxel; Drug: Nab-paclitaxel; Other: Placebo; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Pemetrexed; Drug: BMS-986504

Study type: Interventional

Funder types: Industry

Identifiers

NCT07063745

CA240-0029

U1111-1319-8383 (Other Identifier)

2025-521511-40 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to compare the clinical benefit of the combination of BMS-986504 (a selective MTA-cooperative inhibitor of PRMT5) plus pembrolizumab and chemotherapy versus placebo plus pembrolizumab and chemotherapy in first-line metastatic non-small cell lung cancer participants with homozygous MTAP deletion

Enrollment: 590 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Participants must have Metastatic (Stage IV or recurrent) non-small cell lung cancer (NSCLC) (as defined by the American Joint Committee on Cancer, Ninth Edition) with no prior systemic anti-cancer therapy for metastatic disease.
• Participants must have histologically confirmed diagnosis of NSCLC and homozygous methylthioadenosine phosphorylase (MTAP) deletion or MTAP loss.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Participants must have at least 1 measurable lesion as per RECIST v1.1.

Exclusion Criteria

• Nonsquamous participants must not have documented targetable oncogenic mutation or actionable genetic alterations (AGAs) for which there is a standard of care (SoC) available as first-line (1L) therapy.
• Participants must not have symptomatic brain metastases or spinal cord compression.
• Participants must not have any prior systemic therapy (chemotherapy, immunotherapy, targeted therapy, or biological therapy) for metastatic non-small cell lung cancer (mNSCLC). Note: One cycle of SoC treatment prior to randomization will be allowed for participants who require immediate treatment if clinically indicated.
• Participants must not have any known or suspected impairment of gastrointestinal function that may prohibit the ability to absorb or swallow an oral medication without chewing or crushing.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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590 participants in 6 patient groups, including a placebo group

Arm A: BMS-986504 + Pembrolizumab + Chemotherapy

Active Comparator group

Treatment:

Drug: Pemetrexed

Drug: BMS-986504

Drug: Pembrolizumab

Drug: Carboplatin

Drug: Nab-paclitaxel

Drug: Paclitaxel

Drug: Cisplatin

Arm B: BMS-986504 + Pembrolizumab + Chemotherapy

Active Comparator group

Treatment:

Drug: Pemetrexed

Drug: BMS-986504

Drug: Pembrolizumab

Drug: Carboplatin

Drug: Nab-paclitaxel

Drug: Paclitaxel

Drug: Cisplatin

Arm C: Placebo + Pembrolizumab + Chemotherapy

Placebo Comparator group

Treatment:

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Carboplatin

Other: Placebo

Drug: Nab-paclitaxel

Drug: Paclitaxel

Drug: Cisplatin

Arm D: Placebo + Pembrolizumab + Chemotherapy

Placebo Comparator group

Treatment:

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Carboplatin

Other: Placebo

Drug: Nab-paclitaxel

Drug: Paclitaxel

Drug: Cisplatin

Arm E: BMS-986504 + Pembrolizumab + Chemotherapy

Active Comparator group

Treatment:

Drug: Pemetrexed

Drug: BMS-986504

Drug: Pembrolizumab

Drug: Carboplatin

Drug: Nab-paclitaxel

Drug: Paclitaxel

Drug: Cisplatin

Arm F: Placebo + Pembrolizumab + Chemotherapy

Placebo Comparator group

Treatment:

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Carboplatin

Other: Placebo

Drug: Nab-paclitaxel

Drug: Paclitaxel

Drug: Cisplatin