This study will evaluate DS-1062a 6.0 mg/kg vs docetaxel 75 mg/m^2 in participants with
advanced or metastatic NSCLC without actionable genomic alterations and who have been
previously treated with platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody,
either in combination or sequentially. The study will be divided into 3 periods: Screening
Period, Treatment Period, and Follow-up Period.
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 NSCLC that:
1. Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of randomization
(based on the American Joint Committee on Cancer, Eighth Edition)
2. Has documented negative test results for epidermal growth factor receptor (EGFR)
and anaplastic lymphoma kinase (ALK)
3. Has no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic
tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF), or other actionable
driver oncogenes with approved therapies (actionable genomic alteration)
- Has documentation of radiographic disease progression while on or after receiving the
most recent treatment regimen for advanced or metastatic NSCLC
- Participant 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 chemo/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 chemo/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
- Must undergo a mandatory pre-treatment tumor biopsy procedure or, if available, a
tumor biopsy that was recently collected (within 3 months of Screening) after
completion of the most recent anticancer treatment regimen and of adequate size may be
substituted for the mandatory pre-treatment biopsy procedure collected during
Screening.
- Archival tumor tissue from initial diagnosis is required, to the extent that archival
tumor tissue is available
- 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 Cycle 1 Day 1, 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 Cycle 1 Day 1
- 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 Cycle 1 Day 1
- 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 as monotherapy or in combination with other agents
- 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
- Uncontrolled or significant cardiovascular 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).
- History of myocardial infarction within 6 months before Cycle 1 Day 1
- History of uncontrolled angina pectoris within 6 months before Cycle 1 Day 1
- 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 Cycle 1 Day 1) in order to be eligible.
- History of serious cardiac arrhythmia requiring treatment
- LVEF <50% by ECHO or MUGA scan within 28 days before Cycle 1 Day 1
- Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic
blood pressure >110 mmHg) within 28 days before Cycle 1 Day 1
- 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 of study Cycle 1 Day 1, 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
- Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence
of viral infection within 28 days of Cycle 1 Day 1
- Has other primary malignancies, 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 other primary malignancies, 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
- 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
- Have substance abuse or any other medical conditions such as clinically significant
cardiac or psychological conditions