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All Participants |
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Has relapsed or progressed following local standard treatments or for which no standard treatment is available |
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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 inclusion |
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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 biomarkers |
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Is aged ≥18 years old |
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Has an Eastern Cooperative Oncology Group performance status 0-1 |
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Has a left ventricular ejection fraction (LVEF) ≥50% by either an ECHO or MUGA within 28 days before enrollment |
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Has measurable disease based on RECIST version1.1 |
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Has adequate bone marrow reserve and organ function within 7 days before Cycle 1, Day 1\ |
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Has an adequate treatment washout period prior to Cycle 1, Day 1 |
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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 |
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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 |
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Has a life expectancy of ≥3 months |
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Has no prior treatment with antibody drug conjugate with deruxtecan (including trastuzumab deruxtecan [T-DXd; DS-8201a] and patritumab deruxtecan [HER3-DXd; U31402]) |
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Has no prior treatment with trophoblast cell surface antigen 2 (TROP2)-targeted therapy |
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Additional Inclusion Criteria for NSCLC participants |
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Has a pathologically documented unresectable advanced NSCLC disease not amenable to curative therapy |
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Additional Inclusion Criteria for TNBC participants |
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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) |
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Additional Inclusion Criteria for HR positive, HER2-negative participants |
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Pathologically documented unresectable or metastatic breast cancer that is |
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HER2-negative |
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Positive for estrogen receptor and/or progesterone receptor |
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Is documented refractory or resistant to endocrine therapy |
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Was previously treated with a minimum of 1 and a maximum of 3 prior lines of chemotherapy in the advanced/metastatic setting |
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Additional Inclusion Criteria for Small-cell lung cancer (SCLC) participants |
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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 |
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No prior exposure to topotecan |
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Additional Inclusion Criteria for Endometrial cancer participants |
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Pathologically documented recurrent or persistent endometrial cancer that relapsed or progressed after any established and/or curative therapies, including at least 1 systemic therapy |
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Additional Inclusion Criteria for Pancreatic adenocarcinoma participants |
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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 |
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Additional Inclusion Criteria for HER2-negative gastroesophageal cancer |
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participants |
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Pathologically documented unresectable or metastatic adenocarcinoma of the stomach or esophagus, including the gastroesophagel junction (GEJ) that was previously treated with at least 1 prior line of systemic therapy |
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No known history of HER2-positivity (defined as Immunohistochemistry IHC 3+ or IHC 2+ and in situ hybridization ISH+) as classified by ASCO-CAP at any time |
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Additional Inclusion Criteria for Esophageal cancer participants |
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Pathologically documented unresectable or metastatic squamous cell carcinoma of the esophagus that was previously treated with at least 1 prior line of therapy including platinum-based chemotherapy |
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Additional Inclusion Criteria for Head and neck squamous cell carcinoma (HNSCC) |
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participants |
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Pathologically documented unresectable or metastatic HNSCC that was previously treated |
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with 1-3 prior lines of therapy including platinum and ICI (in combination or |
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sequential), in the advanced or metastatic setting |
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Additional Inclusion Criteria for participants with advanced-stage urothelial cancer |
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Pathologically documented unresectable, locally advanced or metastatic, urothelial |
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Additional Inclusion Criteria for Colorectal cancer (CRC) participants |
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carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) |
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Has not progressed or relapsed within 6 months of therapy with irinotecan |
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of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) that |
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was previously treated with at least 1 prior line of therapy including platinum-based |
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Pathologically documented unresectable or metastatic ovarian cancer that |
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chemotherapy and immune checkpoint inhibitor (in combination or sequential) |
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Has relapsed or progressed within 6 months of platinum-based chemotherapy |
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Pathologically documented unresectable or metastatic CRC that was previously treated |
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with, or were not considered candidates for, available therapies including |
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Pathologically documented unresectable or metastatic ovarian cancer that |
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fluoropyrimidine-based chemotherapy, an anti-vascular. endothelial growth factor |
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therapy, and an anti-epidermal growth factor (EGFR) therapy |
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Additional Inclusion Criteria for Platinum-resistant ovarian cancer participants |
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Is epithelial ovarian (including less-common histologies per National |
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Additional Inclusion Criteria for Cervical cancer participants |
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Comprehensive Cancer Network (NCCN) |
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Additional Inclusion Criteria for Platinum-sensitive ovarian cancer participants |
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Is epithelial ovarian (including less-common histologies per NCCN guidelines) |
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fallopian tube, or primary peritoneal presentation |
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Has relapsed or progressed at least 6 months after the most recent platinum-based |
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chemotherapy |
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Pathologically documented unresectable or metastatic cervical cancer that relapsed or |
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progressed after at least 1 prior line of systemic therapy |
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Additional Inclusion Criteria for Castration-resistant prostate cancer participants |
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Pathologically documented unresectable CRPC that |
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Is adenocarcinoma of the prostate without neuroendocrine differentiation or small cell |
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histology |
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Is surgically or medically castrated, with testosterone levels of less than 50 |
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nanograms per deciliter |
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Objective progression as determined by radiographic progression for participants with |
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measurable disease after androgen deprivation |
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Has relapsed or progressed after at least 1 of the following: abiraterone |
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enzalutamide, apalutamide or darolutamide |
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Has relapsed or progressed after at least 1, but not more than 2, cytotoxic |
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chemotherapy regimens for metastatic CRPC |
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Has at least 1 documented lesion on either a bone scan or a CT/MRI scan |
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Has clinically significant corneal disease
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Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
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Has unresolved toxicities from previous anticancer therapy
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Has leptomeningeal carcinomatosis
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Otherwise considered inappropriate for the study by the investigator
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Has active human immunodeficiency virus (HIV) infection that is not well controlled
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All of the following criteria are required to define an HIV infection that is well
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controlled: undetectable viral RNA load, CD4+ count >250, no history of AIDS-defining
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opportunistic infection within the past 12 months, and stable for at least 4 weeks on
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the same anti-HIV medications. If an HIV infection meets the above criteria
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Has a history of malignancy, other than a tumor type specified in the Inclusion
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monitoring of viral RNA load and CD4+ count is recommended. Subjects/participants must
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Criteria, except (a) adequately resected non-melanoma skin cancer, (b) curatively
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be tested for HIV prior to Cycle 1 Day 1 if acceptable by local regulations or an
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treated in situ disease, or (c) other solid tumors curatively treated, with no
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IRB/IEC
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evidence of disease for ≥3 years
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Has an active or uncontrolled hepatitis B and/or hepatitis C infection, is positive
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Uncontrolled or significant cardiac disease including myocardial infarction or
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for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B
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uncontrolled/unstable angina within 6 months prior to Cycle 1 Day 1
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(hepatitis B surface antigen [HBsAg], anti-hepatitis B surface antibody [anti-HBs]
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History of congestive heart failure (New York Heart Association classes II-IV) or
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anti-hepatitis B core antibody [anti-HBc], or hepatitis B virus [HBV] DNA) and/or
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uncontrolled or significant cardiac arrhythmia, uncontrolled hypertension(resting
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hepatitis C infection (as per HCV RNA) within 28 days of Cycle 1 Day 1
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systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg)
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Has a mean corrected QT interval (QTcF) prolongation to >470 ms based on of the
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screening triplicate 12-lead ECGs
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Has a history of non-infectious interstitial lung disease (ILD)/pneumonitis that
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required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis
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cannot be ruled out by imaging at screening
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Has spinal cord compression or clinically active brain metastases, defined as
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untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to
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control associated symptoms. Participants with clinically inactive brain metastases
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may be included in the study. A minimum of 2 weeks must have elapsed between the end
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of whole brain radiotherapy and study enrollment. Participants with treated brain
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metastases that are no longer symptomatic and who require no treatment with steroids
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may be included in the study if they have recovered from the acute toxic effect of
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radiotherapy
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Is lactating or pregnant as confirmed by pregnancy tests performed within 7 days
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before enrollment
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Has a concomitant medical condition that would increase the risk of toxicity, in the
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opinion of the Investigator
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Has a history of severe hypersensitivity reactions to either the drug substances or
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inactive ingredients of DS-1062a. Has a history of severe hypersensitivity reaction to
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other monoclonal antibodies
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Has any other medical conditions, including cardiac disease or psychological
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disorders, and/or substance abuse that would increase the safety risk to the
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participant or interfere with participation of the participant or evaluation of the
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clinical study in the opinion of the Investigator
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Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
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including, but not limited to, any underlying pulmonary disorder, or any autoimmune
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connective tissue or inflammatory disorders with pulmonary involvement, or prior
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pneumonectomy
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Has substance abuse or any other medical conditions such as clinically significant
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cardiac or psychological conditions, that may, in the opinion of the investigator
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interfere with the participant's participation in the clinical study or evaluation of
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the clinical study results
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Psychological, social, familial, or geographical factors that would prevent regular
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follow-up. Adults under guardianship, curatorship, safeguard of justice, or family
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empowerment measure are not eligible
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