The main objective of the study is to characterize safety and efficacy of 2 dose levels of anvumetostat by investigator, and to evaluate anvumetostat monotherapy efficacy by Blinded Independent Central Review (BICR).

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic or unresectable locally advanced MTAP-deleted (Homozygous deletion of MTAP) NSCLC
• Participants will have received and progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease.
• Either an archival tissue sample or an archival block must be available.
• Life expectancy of greater than 3 months, in the opinion of the investigator.
• Participants who have had brain metastases and have been appropriately treated with radiation therapy or surgery ending at least 14 days before study day 1 are eligible.
• Participants with untreated asymptomatic brain metastases smaller or equal to 2 cm in size (per lesion if more than one) and not requiring corticosteroid treatment are eligible.

Exclusion Criteria:

Disease Related

• Tumors harboring the following mutations amenable to targeted therapies: epidermal growth factor receptor (EGFR), ALK receptor tyrosine kinase (ALK), ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), MET proto-oncogene (MET), B-Raf proto-oncogene (BRAF), RET proto-oncogene (RET), Human epidermal growth factor receptor 2 (HER2/ERBB2), KRAS proto-oncogene G12C (KRAS G12C).

Other Medical Conditions

• Major surgery within 28 days of study day 1.
• Untreated symptomatic central nervous system (CNS) metastatic disease regardless of size or asymptomatic brain metastases greater than 2 cm per lesion.

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.