Inclusion Criteria:

          -  Men or women ≥20 years old in Japan, ≥18 years old in the United States on the day of
             signing the informed consent form (for the other countries, local regulatory
             requirements to consent should be followed)

          -  Advanced or metastatic NSCLC, histologically confirmed at diagnosis of NSCLC,
             documented negative test results for EGFR and ALK genomic alterations, and no known
             genomic alterations in ROS1, NTRK, BRAF, RET, MET, or other driver oncogenes with
             approved therapies (actionable genomic alterations).

          -  Is not a candidate for surgical resection or chemoradiation with curative intent

          -  Documentation of radiological disease progression while on or after receiving the most
             recent treatment regimen, if any, for advanced or metastatic NSCLC.

          -  Must meet the following prior therapy requirements for advanced or metastatic NSCLC:

               -  Dose escalation (all cohorts): Has received ≤ 2 lines of prior anticancer therapy
                  for advanced/metastatic disease

               -  Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with
                  1120 mg durvalumab Q3W): Has not received immune checkpoint inhibitor (ICI)
                  including PD-1/PD-L1, PD-L2, CTLA-4, and may or may not have been treated with
                  systemic chemotherapy for advanced or metastatic NSCLC

               -  Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with
                  1120 mg durvalumab and 4 cycles of AUC 5 carboplatin or cisplatin 75 mg/m^2 Q3W):
                  ICI naïve and has not been treated with systemic anticancer therapy for advanced
                  or metastatic NSCLC.

          -  Willing and able to undergo a mandatory tumor biopsy. There is no requirement for
             PD-L1 protein expression for inclusion.

          -  Archival tumor tissue from initial diagnosis, to the extent that archival tumor tissue
             is available, for measurement of TROP2 expression levels or other biomarkers.

          -  Has adequate bone marrow reserve and organ function at baseline within 7 days prior to
             Cycle 1 Day 1..

        Exclusion Criteria:

          -  Experienced grade 3 or higher immune-related adverse events with prior immunotherapy
             treatment

          -  Received a live vaccine within 30 days prior to the first dose of study treatment.

          -  Active, known, or suspected autoimmune disease.

          -  Has a condition requiring systemic treatment with either corticosteroids (>10 mg daily
             prednisone equivalent) or other immunosuppressive medications within 14 days of Cycle
             1 Day 1.

          -  Prior allogenic organ transplantation

          -  Has a history of severe hypersensitivity reactions to either the drug substances or
             inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd or
             durvalumab, and carboplatin or cisplatin for participants to be enrolled in those
             relevant cohorts)

          -  Uncontrolled or significant cardiac disease

          -  Has spinal cord compression or clinically active central nervous system metastases,
             defined as untreated and symptomatic, or requiring therapy with corticosteroids or
             anticonvulsants to control associated symptoms.

          -  History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required
             steroids, has current ILD/pneumonitis, or where suspected ILD/ pneumonitis cannot be
             ruled out by imaging at screening.

          -  Clinically severe pulmonary compromise resulting from intercurrent pulmonary
             illnesses.

          -  Has a history of malignancy, other than NSCLC, except (a) adequately resected
             nonmelanoma skin cancer, (b) curatively treated in situ disease, or (c) other solid
             tumors curatively treated, with no evidence of disease for ≥3 years.

          -  Toxicities from previous anticancer therapy, defined as toxicities (other than
             alopecia) not yet improved to the National Cancer Institute Common Terminology
             Criteria for Adverse Events version 5.0 Grade ≤1 or baseline