• Has locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation

• Has at least one measurable lesion per RECIST version 1.1

• Has Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening

• Has histologically or cytologically documented adenocarcinoma NSCLC

• Has acquired resistance to EGFR TKI according to the Jackman criteria (PMID: 19949011)

∙ Historical confirmation that the tumor harbors an epidermal growth factor receptor (EGFR) mutation known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (including G719X, exon 19 deletion, L858R, L861Q)

‣ Has experienced clinical benefit from an EGFR TKI, followed by systemic progression of disease \[Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1\] or World Health Organization (WHO)\] while on continuous treatment with an EGFR TKI

• Is currently receiving and able to discontinue erlotinib, gefinitib, afatinib, or osimertinib

• Has been receiving erlotinib, gefitinib, afatinib, or osimertinib for at least 6 weeks with well-controlled related toxicities less than Grade 3 in severity at the time of Screening

• Has radiological documentation of disease progression while receiving continuous treatment with erlotinib, gefitinib, afatinib, or osimertinib

• Is willing to provide archival tumor tissue from a biopsy performed within 6 months of progression during treatment with erlotinib, gefitinib, afatinib, or osimertinib OR has at least one lesion, not previously irradiated, amenable to core biopsy and is willing to undergo screening tumor biopsy

• Demonstrates absence of EGFR T790M mutation if treated with erlotinib, gefitinib, or afatinib. No EGFR mutation testing is required if treated with osimertinib.

• Has received systemic therapy for locally advanced or metastatic disease including at least 1 platinum-based chemotherapy regimen

• Has documented radiological disease progression during/after most recent treatment regimen for locally-advanced or metastatic disease

• For Cohorts 1, 2, 3a, and 3b: Is willing to provide archival tumor tissue from a biopsy performed within 6 months of consent and performed after progression during/after treatment with most recent cancer therapy regimen OR has at least 1 lesion, not previously irradiated, amenable to core biopsy and is willing to undergo tumor biopsy. Tumor tissue must be of sufficient quantity as defined in the laboratory manual and contain adequate tumor tissue content as confirmed by haematoxylin and eosin (H\&S) staining at central laboratory.

‣ For Cohort 4: Neither archival tumor tissue nor core tumor biopsy will be collected

• Has histologically or cytologically documented:

∙ Cohort 1: Adenocarcinoma NSCLC

‣ Cohorts 3a, 3b, and 4: NSCLC (including any histology other than small-cell or combined small cell and non-small cell)

• Has documentation of radiological disease progression following one or more lines of EGFR TKI treatment. Participants with EGFR T790M mutation following treatment with erlotinib, gefitinib afatinib, or dacomitinib must have received and have documentation of radiological disease progression following treatment with osimertinib unless unable or unwilling.

• Has documentation of EGFR-activating mutation(s) detected from tumor tissue: G719X, exon deletion 19, L858R, or L861Q. Participants with other EGFR-activating mutations may be eligible following discussion with the Sponsor.

• Has histologically or cytologically documented squamous or non-squamous NSCLC (ie, without EGFR-activating mutations).

• Has received prior treatment with anti-PD-1 or anti-PD-L1 antibody-based regimen in the locally advanced or metastatic setting unless unable or unwilling. Participants with NSCLC known to harbor a genomic alteration(s) other than EGFR mutation(s) (eg, ALK or ROS1 fusion) for which treatment is available must have also received prior treatment with at least 1 genotype-directed therapy.

• Sign and date the main study ICF, prior to the start of any study-specific qualification procedures. A separate tissue screening consent will be obtained from all participants.

• Male or female subjects aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years old)

• Has locally advanced or metastatic NSCLC not amenable to curative surgery or radiation.

• Has histologically or cytologically documented squamous or nonsquamous NSCLC

• Has documentation of KRAS-G12C mutation(s) detected from tumor tissue or liquid biopsy.

• Has received at least two prior systemic therapies for locally advanced or metastatic disease, including 1 selective KRAS-G12C-targeted therapy (e.g., including as part of a clinical trial) (eg, the combination therapy of KRAS G12C-targeted therapy and immuno-oncology therapy can be considered as 2 prior systemic therapies).

• Has documentation of radiological disease progression according to RECIST v1.1 while either on or following the most recent treatment regimen for locally advanced or metastatic disease.

• Has ≥1 measurable lesion on computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST v1.1 by Investigator assessment that has not been previously irradiated.

• Provides a pretreatment tumor tissue sample of sufficient quantity, as defined in the Study Laboratory Manual.

⁃ ECOG PS 0 or 1 at the time of Screening.

⁃ Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to Cycle 1 Day 1 as specified in the protocol.

⁃ If the participant is a female of childbearing potential, she must have a negative serum pregnancy test at screening and must be willing to use a highly effective birth control upon enrollment, during the Treatment Period, and for 7 months following the last dose of study drug.

⁃ Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the time of final study drug administration.

⁃ If male, the subject must be surgically sterile or willing to use highly effective birth control upon enrollment, during the treatment period, and for at least 4 months following the last dose of study drug.

⁃ Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and for at least 4 months after the final study drug administration.

⁃ Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.