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

1. Has the ability to provide written informed consent by signing and dating
the ICF prior to the start of any study-specific qualification procedures
2. Adults >=18 years
3. Has a life expectancy =3 months based on Investigator's opinion.
4. Has pathologically documented Stage IIIB, IIIC, or Stage IV NSCLC with or
without actionable genomic alteration(s) (AGA) at the time of randomization
(based on the American Joint Committee on Cancer, Eighth Edition) and meets the
following criteria for NSCLC:
a. Subjects Without AGA:
- Subjects must have documented negative test results for EGFR and ALK
genomic alterations. If test results for EGFR and ALK are not available,
subjects are required to undergo testing performed locally for these genomic
alterations.
- Subjects have no known genomic alterations in ROS1, NTRK, BRAF, MET
exon 14 skipping, or RET.
- Subjects with known KRAS mutations (testing during screening is not
mandatory), in the absence of any driver genomic alterations, are eligible and
must meet the prior therapy requirements for subjects without actionable
genomic alterations described below. These subjects must be stratified as NSCLC
without AGA at the time of randomization.
b. Subjects With AGA:
- Subjects must have 1 or more documented actionable genomic alteration: EGFR,
ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
5. Subjects must have documentation of radiographic disease progression while
on or after receiving the most recent treatment regimen for advanced or
metastatic NSCLC
6. Subject must meet the following prior therapy requirements:
Subjects without AGA must meet ONE of the following prior therapy requirements
for advanced or metastatic NSCLC:
a. Received platinum-based chemotherapy in combination with α-PD-
1/α-PD-L1 monoclonal antibody as the only prior line of therapy
OR
b. 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
Subjects with AGA must meet the following prior therapy requirements
for advanced or metastatic NSCLC:
a. Has been treated with 1 or 2 prior lines of applicable targeted therapy that
is locally approved for the subject's genomic alteration at the time of
screening; OR one or more of the agents specified in the protocol
b. Has received platinum-based chemotherapy as the only prior line of cytotoxic
therapy
c. May have received up to one α-PD-1/α-PD-L1 monoclonal antibody alone or in
combination with a cytotoxic agent.
7. 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 subject 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.
Note: Results from the TROP2 testing of the pre-treatment tumor biopsy will not
be used to determine eligibility for the study.
8. Inclusion Criterion removed
9. Has measurable disease based on local imaging assessment using RECIST v1.1
10. Has an Eastern Cooperative Oncology Group performance status ECOG PS) of 0
or1 at Screening
11. Within 7 days before randomization, has adequate bone marrow function as
detailed in the study protocol
12. Within 7 days before randomization, has adequate hepatic function as
detailed in the study protocol
13. Within 7 days before randomization, has adequate renal function, including
mild or moderate renal function, as detailed in the study protocol
14. Has left ventricular ejection fraction (LVEF) >=50% by either ECHO or MUGA
scan within 28 days before randomization
15. Has adequate blood clotting function defined as international normalized
ratio/prothrombin time and either partial thromboplastin or activated partial
thromboplastin time <=1.5 × ULN
16. Has an adequate treatment washout period before randomization, as defined
in the study protocol
For the full list of inclusion criteria, please see protocol section 5.1

1. Has mixed small-cell lung cancer and NSCLC histology
2. Has spinal cord compression or clinically active central nervous system
(CNS) metastases, defined as untreated and symptomatic, or requiring therapy
with corticosteroids or anticonvulsants to control associated symptoms.
Subjects with clinically inactive brain metastases may be included in the
study. Please see additional details in the protocol
3. Has leptomeningeal carcinomatosis or metastasis
4. Had prior treatment with:
a. Any agent, including antibody-drug conjugate (ADC), containing a
chemotherapeutic agent targeting topoisomerase I
b. TROP2-targeted therapy.
c. Docetaxel
5. 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 as described in Inclusion Criterion 6
6. Has NSCLC disease that is eligible for definitive local therapy alone
7. Has uncontrolled or significant cardiac disease as described in detail in
the protocol
8. Has a history of (non-infectious) ILD/pneumonitis that required steroids,
has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled
out by imaging at Screening
9. Clinically severe pulmonary compromise resulting from intercurrent pulmonary
illnesses including, but not limited to, any underlying pulmonary disorder, or
any autoimmune, connective tissue or
inflammatory disorders with pulmonary involvement, or prior pneumonectomy
10. Has significant third-space fluid retention (for example ascites or pleural
effusion) and is not amenable for required repeated drainage
11. Clinically significant corneal disease
12. Uncontrolled infection requiring IV antibiotics, antivirals, or
antifungals; suspected infections (eg, prodromal symptoms); or inabilityto rule
out infections
13. Has known human immunodeficiency virus (HIV) infection that is not well
controlled
14. 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. See section 5.2 of protocol for details.
15. Has a history of malignancy, other than NSCLC except a) adequately resected
non-melanoma skin cancer, b) curatively treated in situ disease, or c) other
solid tumors curatively treated, with no evidence of disease for >=3 years.
16. Concomitant medical condition that would increase the risk of toxicity in
the opinion of the Investigator
17. Toxicities from previous anticancer therapy, defined as toxicities (other
than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade <=1 or baseline
18. Has a history of severe hypersensitivity reactions to either the drug
substances or inactive ingredients (including but not limited to polysorbate
80) of DS-1062a or docetaxel
19. History of severe hypersensitivity reactions to other monoclonal antibodies
20. Is pregnant or breastfeeding or planning to become pregnant

For the full list of exclusion criteria, please see protocol section 5.2.