Inclusion Criteria - 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 1. Participants must have documented evidence of EGFR status. 2. Participants with EGFR mutant or wild type NSCLC are allowed. Exclusion Criteria - 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.