Inclusion Criteria for both Dose Escalation and Dose Expansion:

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

          2. Has at least one measurable lesion per RECIST version 1.1

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

        Inclusion Criteria for Dose Escalation only:

          1. Has histologically or cytologically documented adenocarcinoma NSCLC

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

               1. 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)

               2. 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

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

          4. 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

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

          6. 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

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

        Inclusion Criteria for all cohorts of Dose Expansion only:

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

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

          3. 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.

        Inclusion Criteria specific to Cohort 1, Cohort 3a, and Cohort 3b of Dose Expansion:

          1. Has histologically or cytologically documented:

               1. Cohort 1: Adenocarcinoma NSCLC

               2. Cohort 3a and 3b: NSCLC (including any histology other than small-cell or
                  combined small cell and non-small cell)

          2. 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.

          3. 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.

        Inclusion Criteria specific to Cohort 2 of Dose Expansion:

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

          2. 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.

        Exclusion Criteria for Dose Escalation and Dose Expansion:

          1. Has any evidence of small cell histology, or combined small cell and non-small cell
             histology, in original tumor biopsy or in Screening biopsy performed after progression

          2. Treatment with any of the following:

               1. Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s)
                  from a previous cancer treatment regimen or clinical study (other than EGFR TKI
                  in Cohort 1 only), within 14 days of the first dose of study treatment

               2. Immune checkpoint inhibitor therapy within 21 days of the first dose of study
                  treatment

               3. Prior treatment with an anti-HER3 antibody (dose escalation only)

               4. Prior treatment with a topoisomerase I inhibitor (dose escalation only)

               5. Prior treatment with an antibody-drug conjugate (ADC) that consists of an
                  exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201a) (dose
                  escalation only)

               6. Major surgery (excluding placement of vascular access) within 4 weeks of the
                  first dose of study drug treatment

               7. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field
                  of radiation within 4 weeks of the first dose of study drug treatment, or
                  palliative radiation therapy within 2 weeks of the first dose of study drug
                  treatment, or stereotactic radiotherapy within 1 week prior to the first dose of
                  U3-1402

          3. Has history of other active malignancy within 3 years prior to enrollment, except:

               1. Adequately treated non-melanoma skin cancer OR

               2. Superficial bladder tumors (Ta, Tis, T1) OR

               3. Curatively treated in situ disease

          4. 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. Participants with clinically inactive
             brain metastases may be included in the study. Participants with treated brain
             metastases that are no longer symptomatic and who require no treatment with
             corticosteroids or anticonvulsants may be included in the study if they have recovered
             from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed
             between the end of whole brain radiotherapy and study enrollment (1 week for
             stereotactic radiotherapy)

          5. Has history of myocardial infarction within the past 6 months

          6. Has symptomatic congestive heart failure[New York Heart Association (NYHA) Classes
             II-IV], unstable angina within the past 6 months, or cardiac arrhythmia requiring
             antiarrhythmic treatment

          7. Has left ventricular ejection fraction (LVEF) < 50% by either echocardiogram (ECHO) or
             multigated acquisition scan (MUGA)

          8. Has any clinically important abnormalities in rhythm, conduction or morphology of
             resting electrocardiogram (ECG), eg, complete left bundle branch block, third-degree
             heart block, second-degree heart block, or PR interval > 250 milliseconds (ms)

          9. Has a mean corrected QT interval using Fridericia's Correction Formula (QTcF)
             prolongation to > 470 ms for females and > 450 ms for males in three successive
             Screening measurements

         10. Unable or unwilling to discontinue concomitant drugs that are known to prolong the QT
             interval

         11. Has any factors that increase the risk of corrected QT (QTc) interval prolongation or
             risk of arrhythmic events, such as congenital long QT syndrome, family history of long
             QT syndrome, or unexplained sudden death under 40 years of age in first-degree
             relatives.

         12. Has any history of interstitial lung disease (ILD) (including pulmonary fibrosis or
             severe radiation pneumonitis), has current ILD/pneumonitis, or is suspected to have
             such disease by imaging during screening

         13. Has clinically significant corneal disease

        Additional Exclusion Criteria for Dose Expansion Cohort 2:

        1. Has documentation of one or more of the following EGFR-activating mutations: G719X, exon
        19 deletion, L858R, or L861Q