A Randomized, Open-Label, Phase 3 Study of Setidegrasib versus Docetaxel in Participants with KRAS G12D-Mutated Locally Advanced (Unresectable) or Metastatic Non-small Cell Lung Cancer Who Have Progressed on or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy.

Inclusion Criteria: - Participant has histologically confirmed locally advanced (unresectable) or metastatic non-small cell lung cancer (NSCLC) with documented Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutation result status, based on local or central testing. - The participant's positive KRAS G12D mutation result (either in tumor tissue or plasma ctDNA) must be available prior to randomization. - If the participant is enrolling based on a local testing result, the result may have been based on tissue or liquid (blood) testing. If the participant is enrolling via central testing, the eligibility sample must be from tissue. - Participant must have progressed or experienced disease recurrence on or after platinum based chemotherapy (which includes but is not limited to platinum combinations with pemetrexed, paclitaxel, etoposide or gemcitabine) in combination with anti-PD-1/PD-L1 antibody OR platinum-based chemotherapy and anti-PD-1/PD-L1 antibody (in either order) sequentially in the locally advanced (unresectable) or metastatic setting (participant who received anti PD-1/anti-PD-L1 antibody or platinum-based chemotherapy as first-line therapy in the locally advanced [unresectable] or metastatic setting may have received the combination of platinum-based chemotherapy and anti PD1/anti PD L1 antibody in the second line locally advanced [unresectable] or metastatic setting). - No additional treatments are allowed in the locally advanced (unresectable) or metastatic setting, with the exception of: Anti-vascular endothelial growth factor (VEGF) therapy (e.g., bevacizumab), when administered in combination with platinum-based chemotherapy and/or anti-PD-1/PD-L1 as part of a standard regimen in the locally advanced (unresectable) or metastatic setting and - Anti-CTLA-4 antibodies (e.g., ipilimumab, tremelimumab), when administered in combination with anti-PD-1/PD-L1 (with or without platinum-based chemotherapy) as part of a standard regimen in the locally advanced (unresectable) or metastatic setting. - For the purposes of eligibility, for a participant who has received prior neoadjuvant or adjuvant therapy and has had recurrence during or within 6 months of completion of therapy, the neoadjuvant or adjuvant therapy will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting (for those who received perioperative therapy, the entire course will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting). - For the purposes of eligibility, for a participant with a history of unresectable Stage III disease who has received prior multi-modal therapy and has had recurrence on or within 6 months of completion of therapy, the multi-modal therapy will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting. If chemoradiation was followed by treatment with checkpoint inhibitor therapy (CPI) without documented progression between chemoradiation and CPI, the entire treatment course will be counted as a line of systemic therapy in the locally advanced (unresectable) or metastatic setting, for the purposes of eligibility. - Maintenance therapy following platinum doublet-based chemotherapy is not considered a separate line of therapy. - Female participant is not pregnant and at least 1 of the following conditions apply: - Not a woman of childbearing potential (WOCBP). - WOCBP who has a negative urine or serum pregnancy test at screening (Specific to Japan: with a medical interview) and agrees to follow the contraceptive guidance from the time of informed consent through ≥ 6 months after the final setidegrasib administration or ≥ 2 months after the final docetaxel administration, as applicable. - Must not be breastfeeding or lactating starting at screening and throughout the investigational period and for ≥ 6 months after the final setidegrasib administration or ≥ 2 months after the final docetaxel administration, as applicable. (Note that this is stricter than some docetaxel product information/labeling documents due to the uncertainty regarding excretion of docetaxel in human milk.) - Must not donate ova starting at first administration of study intervention and throughout the investigational period and for ≥ 6 months after the final setidegrasib administration or ≥ 2 months after the final docetaxel administration, as applicable. - Participant consents to and provides a baseline tumor tissue and plasma specimen during prescreening and/or screening. - Participant has an ECOG performance status of 0 or 1 within 7 days prior to randomization. Exclusion Criteria: - Participant has known untreated or symptomatic central nervous system (CNS) metastases. Participant with previously treated brain metastases may be eligible if they have stable CNS disease for ≥ 2 weeks prior to randomization, all neurologic symptoms have returned to baseline, there is no evidence of new or enlarging brain metastases on brain imaging performed within 28 days prior to randomization and they are receiving ≤ 10 mg/day of prednisone or equivalent. Participants with untreated CNS metastases, even if asymptomatic, are not eligible. - Participant has mixed small-cell lung cancer and NSCLC histology. - Participant has leptomeningeal disease as a manifestation of the current malignancy. - Participant has another prior malignancy active (i.e., requiring treatment, including hormonal therapies, or intervention) within the previous 2 years different from the primary malignancy for this study, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed. - Participant has known hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen [HBsAg]-positive or anti HBV core antibody-positive) or known hepatitis C virus (HCV) (defined as HCV RNA [qualitative] detected) infection. - Participant with human immunodeficiency virus (HIV) infection may be eligible if the participant has not had an opportunistic infection within the past 12 months. Participant must be on established antiretroviral therapy for ≥ 4 weeks, have a CD4+ T cell ≥ 200 cells/µL and must have an HIV viral load < 400 copies/mL prior to randomization (HIV testing is not required unless mandated by the local health authority). - Participant has current grade ≥ 2 peripheral neuropathy. - Participant has uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Participant with PleurX catheters in place may be considered for the study with medical monitor approval. - Participant has received therapeutic or palliative radiation therapy within 14 days prior to randomization (see first Exclusion Criteria for CNS metastases); participant must have recovered from all radiotherapy related toxicity to ≤ grade 1, with the exception of alopecia (any grade of alopecia allowed). - Participant has a known actionable mutation for which an approved targeted therapy is locally available, including, but not limited to, KRAS G12C mutation, EGFR mutation (exon 19 deletions, exon 21 L858R point mutation, T790M, exon 20 insertion), ALK or ROS1 rearrangement, NTRK fusion, NRG1 fusion, BRAF V600E mutation, MET exon 14 skipping mutation, RET rearrangement or HER2 activating mutation. - Participant has received prior treatment with either docetaxel or a KRAS-targeting agent (including KRAS directed inhibitors, degraders, siRNA, vaccines and cellular therapies). - Participant requires treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450 (CYP)3A or CYP2D6 or strong inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1) or organic anion transporting polypeptide 1B3 (OATP1B3).