A Study of Navlimetostat (BMS-986504) Alone or in Combination With Izalontamab Brengitecan in Participants With Pre-treated Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) With Homozygous MTAP Deletion or MTAP Loss (MountainTAP-9)

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Histologically confirmed diagnosis of NSCLC and homozygous MTAP deletion detected in tumor tissue and willingness to provide archival/fresh samples at screening for central MTAP status confirmation.
• Advanced or metastatic NSCLC not amenable to curative therapies after progression on prior therapies at the time of enrollment (based on the American Joint Committee on Cancer, Ninth Edition).
• At least 1 measurable lesion as per RECIST v1.1.
• Documented radiographic disease progression on or after the most recent line of treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Participant must be ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the ICF.
• Capability to swallow tablets intact (without chewing or crushing).
• For combination arms
• Participants must have documented evidence of EGFR status.
• Participants with EGFR mutant or wild type NSCLC are allowed.

You cannot join if

• Active brain metastases or carcinomatous meningitis.
• History of gastrointestinal disease or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications.
• Prior treatment with a PRMT5 or MAT2A inhibitor.
• Known severe hypersensitivity to study treatment and/or any of its excipients.
• For combination arms
• a. Prior therapy with iza-bren or any other antibody and/or ADC targeting EGFR and/or HER3 or containing a topoisomerase 1 inhibitor payload, except amivantamab.
• Other protocol-defined inclusion/exclusion criteria apply.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

PRMT5-MTA inhibitor MRTX1719. An orally bioavailable inhibitor of the protein arginine methyltransferase 5 (PRMT5)-methylthioadenosine (MTA) complex, with potential antineoplastic activity. Upon oral administration, PRMT5-MTA inhibitor MRTX1719 selectively binds to the PRMT5-MTA complex that is elevated in methylthioadenosine phosphoylase (MTAP)-deleted cancer cells, thereby specifically inhibiting the function of PRMT5 solely within MTAP-deleted cancer cells and not in normal, healthy cells. By inhibiting the methyltransferase activity of PRMT5, levels of both monomethylated and dimethylated arginine residues in histones H2A, H3 and H4 are decreased. This modulates the expression of genes involved in several cellular processes, including cellular proliferation. This may increase the expression of antiproliferative genes and/or decrease the expression of genes that promote cell proliferation, which may lead to decreased growth of rapidly proliferating cancer cells. MRTX1719 also causes dysregulated RNA splicing and decreased pRb. Together, this decreases proliferation and increases apoptosis specifically in MTAP-deleted cancer cells. PRMT5, a type II methyltransferase that catalyzes the formation of both omega-N monomethylarginine (MMA) and symmetric dimethylarginine (sDMA) on histones and a variety of other protein substrates involved in signal transduction and cellular transcription, is essential for the viability of cancer and normal cells. It is overexpressed in several neoplasms. Elevated levels are associated with decreased patient survival. MTAP is deleted in certain cancer cells leading to an accumulation of the metabolite MTA; MTA binds to and partially inhibits the activity of PRMT5. NCI Drug Dictionary

izalontamab. An immunoglobulin G (IgG) bispecific antibody targeting both the epidermal growth factor receptor (EGFR; HER1; ErbB1) and the epidermal growth factor receptor 3 (HER3; ErbB3), with potential antineoplastic activity. Upon administration, izalontamab simultaneously targets and binds to EGFR and HER3 expressed on cancer cells, thereby preventing receptor phosphorylation. This prevents the activation of both EGFR- and HER3-mediated signaling pathways and results in the inhibition of tumor cell proliferation. EGFR and HER3, both upregulated and/or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation. NCI Drug Dictionary

Treatments listed in the registry

• BMS-986504 (Drug): Specified dose on specified days
• Izalontamab Brengitecan (Drug): Specified dose on specified days

Randomized · Sequential · masking: None

Main goals

• Number of participants who achieve Objective Response (OR) utilizing the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Up to 3 years after the last participant's last dose of study treatment)
• Number of participants with adverse events meeting protocol defined dose limiting toxicities (DLTs) criteria (Up to 28 days after the last dose of study treatment)
• Number of participants with adverse events (AE) (Up to 28 days after the last dose of study treatment)
• Number of participants with Serious AEs (SAEs) (Up to 28 days after the last dose of study treatment)
• Number of participants with treatment related AEs (Up to 28 days after the last dose of study treatment)
• Number of participants with treatment related SAEs (Up to 28 days after the last dose of study treatment)
• Number of participants with AEs leading to study treatment discontinuation (Up to 28 days after the last dose of study treatment)
• Number of participants with AEs leading to death (Up to 28 days after the last dose of study treatment)
• Number of participants with laboratory abnormalities (Up to 28 days after the last dose of study treatment)

Other goals

• Number of participants who achieve disease control (DC) as assessed by RECIST v1.1
• Number of participants who achieve clinical benefit (CB) as assessed by RECIST v1.1
• Duration of response (DOR) as assessed by RECIST v1.1
• Progression-free survival (PFS) as assessed by RECIST v1.1
• Time to objective response (TTOR) as assessed by RECIST v1.1
• Number of participants with adverse events (AE)
• Number of participants with Serious AEs (SAEs)
• Number of participants with AEs leading to dose interruption, reduction, or discontinuation
• Number of deaths
• Number of participants who achieve Objective Response (OR) as assessed by RECIST v1.1
• Overall Survival (OS)
• Change from baseline in cancer-related symptoms and health-related quality of life as assessed by the Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) total score and symptom score
• Change from baseline in cancer-related symptoms and health-related quality of life as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core Function Global Health Status score
• Change from baseline in cancer-related symptoms and health-related quality of life as assessed by the EORTC-QLQ-F17 quality-of-life (QoL) functional scale score

Planned enrollment: 182 (estimated).

• Dana-Farber Cancer Institute, Boston, Massachusetts
• Karmanos Cancer Institute, Detroit, Michigan
• Washington University School of Medicine, St Louis, Missouri
• Memorial Sloan Kettering Cancer Center, New York, New York
• Gabrail Cancer Center, Canton, Ohio
• Providence Portland Medical Center, Portland, Oregon
• Oregon Health and Science University, Portland, Oregon
• Fred Hutchison Cancer Center, Seattle, Washington
• Medical College of Wisconsin, Milwaukee, Wisconsin

56 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06855771
• NCI Drug Dictionary: C187048
• NCI Drug Dictionary: C203048

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 17, 2026. Public record; not medical advice.