PHASE 3 RANDOMIZED STUDY OF DS-1062A VERSUS DOCETAXEL IN PREVIOUSLY TREATED ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER WITH OR WITHOUT ACTIONABLE GENOMIC ALTERATIONS (TROPION-LUNG01)

This study will evaluate the efficacy, safety, and pharmacokinetics of DS-1062a versus
docetaxel in participants with previously treated advanced or metastatic non-small cell lung
cancer (NSCLC) with or without actionable genomic alterations.

Inclusion Criteria:

Participants eligible for inclusion in the study must meet all inclusion criteria within 28
days of randomization into the study.

- Sign and date the inform consent form (ICF) prior to the start of any study specific
qualification procedures.

- Adults ≥18 years (if the legal age of consent is >18 years old, then follow local
regulatory requirements)

- Life expectancy ≥3 months

- Has pathologically documented Stage IIIB, IIIC, or stage IV NSCLC disease with or
without actionable genomic alterations (AGA) at the time of randomization (based on
the American Joint Committee on Cancer, Eighth Edition) and meets following criteria
for NSCLC:

- Participants without AGA:

1. Must have documented negative test results for epidermal growth factor receptor
(EGFR) and anaplastic lymphoma kinase (ALK).

2. Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1),
neurotrophic tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF),
mesenchymal-epithelial transition (MET) exon 14 skipping, or rearranged during
transfection (RET).

- Participants with AGA must have one or more documented actionable genomic
alteration(s): EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.

- Has documentation of radiographic disease progression while on or after receiving the
most recent treatment regimen for advanced or metastatic NSCLC.

- Participant without AGA must meet 1 of the following prior therapy requirements for
advanced or metastatic NSCLC:

1. Received platinum-based chemotherapy in combination with α-PD-1/α-PD-L1
monoclonal antibody as the only prior line of therapy.

- Includes participants who received prior platinum-based/chemotherapy with or
without radiotherapy with maintenance α-PD-1/α-PD-L1 monoclonal antibody for
Stage III disease and relapsed/progressed within 6 months from the last dose
of platinum-based chemotherapy.

- Includes participants who received prior platinum-based/chemotherapy with or
without radiotherapy (with or without maintenance α-PD-1/α-PD-L1 monoclonal
antibody) for Stage III disease and subsequently received α-PD-1/α-PD-L1
monoclonal antibody therapy (with or without platinum-based chemotherapy)
for recurrent disease.

2. Received platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody (in
either order) sequentially as the only 2 prior lines of therapy.

- Participants with AGA must meet the following for advanced or metastatic NSCLC:

1. Participants who have been treated with 1 or 2 prior lines of applicable targeted
therapy that is locally approved for the participant's genomic alteration at the
time of screening;

- Participants who have tumors with EGFR L858R or exon 19 deletion mutations
must have received prior Osimertinib.

- Those who received a targeted agent as adjuvant therapy for early-stage
disease must have relapsed or progressed while on the treatment or within 6
months of the last dose OR received at least one additional course of
targeted therapy for the same genomic alteration (which may or may not be
same agent used in the adjuvant setting) for relapsed/progressive disease.

- Participants who have been treated with a prior TKI must receive additional
approved targeted therapy, if locally available and clinically appropriate,
for the applicable genomic alteration, or the participant will not be
allowed in the study.

2. Participants who have received platinum-based chemotherapy as the only prior line
of cytotoxic therapy:

- One platinum-containing regimen for advanced disease

- Those who received a platinum-containing regimen as adjuvant therapy for
early-stage disease must have relapsed or progressed while on the treatment
or within 6 months of the last dose OR received at least one additional
course of platinum-containing therapy (which may or may not be same as in
the adjuvant setting) for relapsed/progressive disease.

3. May have received up to one α-PD-1/α-PD-L1 monoclonal antibody alone or in
combination with a cytotoxic agent.

- Must undergo a pre-treatment tumor biopsy procedure or if available, tumor tissue
previously retrieved from a biopsy procedure performed within 2 years prior to the
participant signing informed consent and that has a minimum of 10 × 4 micron sections
or a tissue block equivalent of 10 × 4 micron sections may be substituted for the
pre-treatment biopsy procedure during Screening. If a documented law or regulation
prohibits (or does not approve) sample collection, then such samples will not be
collected/submitted

- Measurable disease based on local imaging assessment using RECIST v1.1

- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening

- Within 7 days before randomization, has adequate bone marrow, hepatic, and renal
function

- Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or
multigated acquisition (MUGA) scan within 28 days before randomization

- Adequate blood clotting function defined as international normalized ratio/prothrombin
time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 ×
upper limit of normal (ULN)

- Adequate treatment washout period before randomization

- Females of childbearing potential must have a negative serum pregnancy test at
screening and must be willing to use highly effective birth control from the time of
enrollment up to 7 months after the last dose of DS-1062a or for at least 6 months
after the last dose of docetaxel

- Males must be surgically sterile or must use a condom in addition to highly effective
birth control if his partners are of reproductive potential from the time of
enrollment and for at least 4 months after last dose of DS-1062a or for at least 6
months after the last dose of docetaxel

- Male participants must not freeze or donate sperm from the time of Screening and
throughout the study period and for at least 4 months after the last dose of DS-1062a
or for at least 6 months after the last dose of docetaxel

- Female participants must not donate, or retrieve for their own use, ova from the time
of Screening and throughout the study period and for at least 7 months after the last
dose of DS-1062a and for at least 6 months after the last dose of docetaxel

Exclusion Criteria:

- Mixed small-cell lung cancer (SCLC) and NSCLC histology

- 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 who 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.

- Has leptomeningeal carcinomatosis or metastasis

- Had prior treatment with:

- Any agent including antibody drug conjugate (ADC) containing a chemotherapeutic
agent targeting topoisomerase I

- TROP2-targeted therapy

- Docetaxel

- Had prior treatment with platinum-based chemotherapy and prior immunotherapy for Stage
II NSCLC disease (eg, in the neo-adjuvant or adjuvant setting) without subsequently
meeting the prior therapy requirements for Stage III or metastatic NSCLC disease

- Has NSCLC disease that is eligible for definitive local therapy alone

- Has uncontrolled or significant cardiac disease, including:

- Mean QT interval corrected for heart rate using Fridericia's formula >470 msec
(based on the average of Screening triplicate 12-lead electrocardiogram [ECG]
determinations).

- Myocardial infarction or uncontrolled/unstable angina within 6 months before
randomization

- Congestive heart failure (CHF) (New York Heart Association Class II to IV) at
Screening. Participants with a history of Class II to IV CHF prior to Screening,
must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA
scan within 28 days before randomization) in order to be eligible.

- Uncontrolled or significant cardiac arrhythmia

- LVEF <50% by ECHO or MUGA scan within 28 days before randomization

- Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic
blood pressure >110 mmHg) within 28 days before randomization

- Has a 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
including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli
within 3 months before randomization, severe asthma, severe chronic obstructive
pulmonary disease, restrictive lung disease, pleural effusion, etc.), or any
autoimmune, connective tissue or inflammatory disorders with pulmonary involvement
(ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior
pneumonectomy.

- Significant third-space fluid retention (for example ascites or pleural effusion) and
is not amenable for required repeated drainage

- Clinically significant corneal disease

- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected
infections (eg, prodromal symptoms); or inability to rule out infections

- Has known human immunodeficiency virus (HIV) infection that is not well controlled

- Has an active or uncontrolled hepatitis B and/or hepatitis C infection, is positive
for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B
(hepatitis B surface antigen [HBsAg], anti-hepatitis B surface antibody [anti-HBs],
anti-hepatitis B core antibody [anti-HBc], or hepatitis B virus [HBV] DNA), and/or
hepatitis C infection (as per hepatitis C virus [HCV] RNA) within 28 days of
randomization.

- Has a history of malignancy, other than NSCLC, except adequately resected non-melanoma
skin cancer, curatively treated in situ disease, or 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 NCI-CTCAE version 5.0 Grade ≤1 or baseline

- Has a history of severe hypersensitivity reactions to either the drug substances,
inactive ingredients (including but not limited to polysorbate 80) of DS-1062a or
docetaxel, or monoclonal antibodies

- Pregnant or breastfeeding

- Has substance abuse or any other medical conditions such as clinically significant
cardiac or psychological conditions