The dosage strength will change during the study but all participants will receive the same
study drug. So the study is not a true 2-arm study, it is a 2-part study.
In both parts, participants with pathologically documented unresectable advanced NSCLC and
triple negative breast cancer (TNBC) who have been refractory to or relapsed from standard
treatment or for which no standard treatment is available, will be enrolled. In Dose
Expansion, additional indications (hormone receptor [HR]-positive human epidermal growth
factor receptor 2 [HER2]-negative breast cancer, small cell lung cancer [SCLC], endometrial
cancer, pancreatic adenocarcinoma, HER2-negative gastric/gastroesophageal junction [GEJ]
cancer, esophageal cancer, head and neck squamous cell carcinoma [HNSCC], transitional cell
carcinoma of the urothelium, colorectal cancer [CRC], platinum-resistant ovarian cancer,
platinum-sensitive ovarian cancer, cervical cancer, and castration-resistant prostate cancer
[CRPC]) may be evaluated, if the study treatment demonstrates acceptable safety, tolerability
and efficacy in NSCLC participants. After the primary analysis, the main (registered) study
will be considered complete, but data will be collected from participants who continue
receiving study drug.
- Has relapsed or progressed following local standard treatments or for which no
standard treatment is available.
- Consents to provide mandatory pre-treatment tumor tissue samples for the measurement
of TROP2 and other biomarkers. There is no minimum TROP2 expression level required for
- Consents to undergo mandatory on-treatment biopsy if clinically feasible and not
contraindicated at the time of on-treatment biopsy, and consents to provide the tumor
tissue samples from on-treatment biopsy for the measurement of TROP2 level and other
- Is aged ≥20 years old in Japan or ≥18 years old in other countries.
- Has an Eastern Cooperative Oncology Group performance status 0-1.
- Has a left ventricular ejection fraction (LVEF) ≥50% by either an ECHO or MUGA within
28 days before enrollment.
- Has measurable disease based on RECIST version1.1.
- Has adequate bone marrow reserve and organ function within 7 days before Cycle 1, Day
- Has an adequate treatment washout period prior to Cycle 1, Day 1.
- If of reproductive/childbearing potential, agrees to use a highly effective from of
contraception or avoid intercourse during and upon completion of the study and for at
least 7 months for females and 4 months for males after the last dose of study drug,
and agrees not to retrieve, freeze or donate sperm or ova starting at Screening and
throughout the study period, and at least 7 months for males and 4 months for males
after the final study drug administration.
- After being fully informed about their illness and the investigative nature of the
protocol (including foreseeable risks and possible toxicities), is willing and able
comply with the protocol and to provide written, ethics committee-approved informed
consent form before performance of any study-specific procedures or examinations.
- Has a life expectancy of ≥3 months.
- Has no prior treatment with antibody drug conjugate with deruxtecan (including
trastuzumab deruxtecan [T-DXd; DS-8201a] and patritumab deruxtecan [HER3-DXd; U31402])
- Has no prior treatment with trophoblast cell surface antigen 2 (TROP2)-targeted
NSCLC participants only:
- Has a pathologically documented unresectable advanced NSCLC disease not amenable to
TNBC participants only:
- Has a pathologically documented advanced/unresectable or metastatic breast cancer with
HR- (estrogen and progesterone receptor) negative disease and HER2 negative expression
according to the American Society of Clinical Oncology - College of American
Pathologists guidelines (ASCO-CAP)
HR positive, HER2-negative participants only:
- Pathologically documented unresectable or metastatic breast cancer that is:
- Positive for estrogen receptor and/or progesterone receptor
- Is documented refractory or resistant to endocrine therapy
- Was previously treated with a minimum of 1 and a maximum of 3 prior lines of
chemotherapy in the advanced/metastatic setting
Small-cell lung cancer (SCLC) participants only:
- Pathologically documented unresectable or metastatic, and/or extensive-stage SCLC that
was previously treated with 1 to 2 prior lines of therapy including platinum-based
chemotherapy and immune checkpoint inhibitor
- No prior exposure to topotecan
Endometrial cancer participants only:
- Pathologically documented recurrent or persistent endometrial cancer that relapsed or
progressed after any established and/or curative therapies, including at least 1
Pancreatic adenocarcinoma participants only:
- Pathologically documented unresectable or metastatic pancreatic cancer that was
previously treated with at least 1 prior line of systemic therapy in neoadjuvant,
adjuvant, locally advanced or metastatic setting
HER2-negative gastric/GEJ cancer participants only:
- Pathologically documented unresectable or metastatic gastric/GEJ adenocarcinoma that
was previously treated with at least 1 prior line of systemic therapy
- No known history of HER2-overexpression (Immunohistochemistry [IHC] 0, IHC 1 or IHC
2+/ in situ hybridization [ISH]-negative) as classified by ASCO-CAP at any time
Esophageal cancer participants only:
- Pathologically documented unresectable or metastatic esophageal cancer that:
- Is squamous or adenocarcinoma
- Was previously treated with at least 1 prior line of therapy including
Head and neck squamous cell carcinoma (HNSCC) participants only:
- Pathologically documented unresectable or metastatic HNSCC that was previously treated
with 1-3 prior lines of therapy including platinum and ICI (in combination or
sequential), in the advanced or metastatic setting
Transitional cell carcinoma of the urothelium participants only:
- Pathologically documented unresectable, locally advanced or metastatic, transitional
cell carcinoma (transitional cell and mixed transitional/non-transitional cell
histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and
urethra) that was previously treated with at least 1 prior line of therapy including
platinum-based chemotherapy and ICI (in combination or sequential).
- Was previously treated with enfortumab vedotin where available
Colorectal cancer (CRC) participants only:
- Pathologically documented unresectable or metastatic CRC that was previously treated
with, or were not considered candidates for, available therapies including
fluoropyrimidine-based chemotherapy, an anti-vascular endothelial growth factor
therapy, and an anti-epidermal growth factor (EGFR) therapy
- Has not progressed or relapsed within 6 months of therapy with irinotecan
Platinum-resistant ovarian cancer participants only:
- Pathologically documented unresectable or metastatic ovarian cancer that:
- Is epithelial ovarian (including less-common histologies per National
Comprehensive Cancer Network (NCCN)
- Has relapsed or progressed within 6 months of platinum-based chemotherapy
Platinum-sensitive ovarian cancer participants only:
- Pathologically documented unresectable or metastatic ovarian cancer that:
- Is epithelial ovarian (including less-common histologies per NCCN guidelines),
fallopian tube, or primary peritoneal presentation
- Has relapsed or progressed at least 6 months after the most recent platinum-based
Cervical cancer participants only:
- Pathologically documented unresectable or metastatic cervical cancer that relapsed or
progressed after at least 1 prior line of systemic therapy
Castration-resistant prostate cancer participants only:
- Pathologically documented unresectable or metastatic CRPC that:
- Is adenocarcinoma of the prostate without neuroendocrine differentiation or small
- Is surgically or medically castrated, with testosterone levels of less than 50
nanograms per deciliter
- Objective progression by RECIST version 1.1 criteria for participants with
measurable disease after androgen deprivation
- Has relapsed or progressed after at least 1 of the following: abiraterone or
- Has relapsed or progressed after at least 1, but not more than 2, cytotoxic
chemotherapy regimens for metastatic castration resistant prostate cancer
(mCRPC). At least 1 regimen must have contained a taxane. If a specific taxane
was used more than once, the regimens containing the same taxane would be
considered as 1 regimen in total.
- Has a history of malignancy, other than a tumor type specified in the Inclusion
Criteria, 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.
- Has a history of myocardial infarction or unstable angina within 6 months before
- Has a medical history of congestive heart failure (New York Heart Association classes
II-IV) or a serious cardiac arrhythmia requiring treatment.
- Has a mean corrected QT interval (QTcF) prolongation to >470 ms based on average of
the screening triplicate 12-lead ECGs.
- 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
- Has clinically significant corneal disease.
- Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
- Has active human immunodeficiency virus infection that is uncontrolled (increasing
plasma HIV RNA viral load) with medication, or has an active hepatitis B or C
- Has spinal cord compression or clinically active brain metastases, defined as
untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to
control associated symptoms. Participants with clinically inactive brain metastases
may be included in the study. A minimum of 2 weeks must have elapsed between the end
of whole brain radiotherapy and study enrollment. Participants with treated brain
metastases that are no longer symptomatic and who require no treatment with steroids
may be included in the study if they have recovered from the acute toxic effect of
- Is lactating or pregnant as confirmed by pregnancy tests performed within 7 days
- Has unresolved toxicities from previous anticancer therapy.
- Has a concomitant medical condition that would increase the risk of toxicity, in the
opinion of the Investigator.
- Has a history of severe hypersensitivity reactions to either the drug substances or
inactive ingredients of DS-1062a.
- Has any other medical conditions, including cardiac disease or psychological
disorders, and/or substance abuse that would increase the safety risk to the
participant or interfere with participation of the participant or evaluation of the
clinical study in the opinion of the Investigator.
- 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