First-in-human Study of DS-1062a for Advanced Solid Tumors (TROPION-PanTumor01)

Running, not enrolling · Phase 1

Conditions studied: Hormone Receptor Positive Breast Cancer, Triple Negative Breast Cancer, Non-small Cell Lung Cancer

In brief

This study is one single group of participants with non-small cell lung cancer (NSCLC) who have not been cured by other treatments. It is the first time the drug has been used in humans. There will be two parts and a sub-study. The primary purpose of the parts are: * Dose Escalation: To investigate the safety and tolerability and to determine the maximum tolerated dose (MTD) and the recommended dose for expansion (RDE) of DS-1062a * Dose Expansion: To investigate the safety and tolerability of DS-1062a in additional solid tumors This study is expected to last approximately 6 years from the time the first participant is enrolled to the time the last subject is off the study. Study sites are located in both the United States and Japan. The number of treatment cycles is not fixed in this study. Participants who continue to benefit from the study treatment may continue, unless: * they withdraw * their disease gets worse * they experience unacceptable side effects. The primary purpose of the sub-study is to compare the effectiveness of steroid versus non-steroid mouthwash as prophylaxis against oral mucositis/stomatitis in participants receiving DS-1062a. The sub-study is a randomized study that will include approximately 76 participants enrolling into the Dose Expansion part.

Key facts

Study ID

NCT03401385

Run by

Daiichi Sankyo Co., Ltd.

People needed

890

Starts

2018-01-31

Expected to finish

2027-01-01

Last updated by the study team

2025-10-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• All Participants:
• 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 inclusion.
• 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.
• Is aged ≥18 years old.
• 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 1.
• 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/or patritumab deruxtecan [HER3-DXd; U3-1402]) and/or ifinatamab deruxtecan [I-DXd; DS-7300]. (Note: Participants in the new HR-positive HER2-low breast cancer cohort is required to have prior treatment with T-DXd and must not have been treated with any other deruxtecan ADC besides T-DXd.)
• Has no prior treatment with trophoblast cell surface antigen 2 (TROP2)-targeted therapy.
• Additional Inclusion Criteria for NSCLC participants:
• Has a pathologically documented unresectable advanced NSCLC disease not amenable to curative therapy.
• Additional Inclusion Criteria for TNBC participants:
• 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).
• Additional Inclusion Criteria for HR positive, HER2-negative participants:
• Pathologically documented unresectable or metastatic breast cancer that is:
• HER2-negative
• 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

You may not qualify if…

• 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.
• Uncontrolled or significant cardiac disease including myocardial infarction or uncontrolled/unstable angina within 6 months prior to Cycle 1 Day 1.
• History of congestive heart failure (New York Heart Association classes II-IV) or uncontrolled or significant cardiac arrhythmia, uncontrolled hypertension(resting systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg).
• Has a mean corrected QT interval (QTcF) prolongation to >470 ms based on of the screening triplicate 12-lead ECGs.
• 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.
• Has clinically significant corneal disease.
• Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Has active human immunodeficiency virus (HIV) infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ count >350, no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications. If an HIV infection meets the above criteria, monitoring of viral RNA load and CD4+ count is recommended. Subjects/participants must be tested for HIV during the Screening Period if acceptable by local regulations or an IRB/IEC.
• Has an active or uncontrolled hepatitis B and/or hepatitis C infection.
• 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 radiotherapy.
• Is lactating or pregnant as confirmed by pregnancy tests performed within 7 days before enrollment.
• 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 a history of severe hypersensitivity reaction to other monoclonal antibodies.
• 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 pneumonectomy.
• Has leptomeningeal carcinomatosis.
• Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the participant's participation in the clinical study or evaluation of the clinical study results.
• Psychological, social, familial, or geographical factors that would prevent regular follow-up. Adults under guardianship, curatorship, safeguard of justice, or family empowerment measure are not eligible.
• Otherwise considered inappropriate for the study by the investigator.
• Additional Exclusion Criteria for Sub-study:
• Has had any prior oral mucositis/stomatitis that did not resolve within 3 months of signing the ICFs
• Requires oral steroid or steroid nasal spray or inhaler for asthma, chronic obstructive pulmonary disease, or any other reason at the time of randomization
• Requires immunosuppressive drugs at the time of randomization
• Has oral inflammation or infections, including candidiasis (thrush) at the time of randomization
• Has a history of severe hypersensitivity reactions or any other contraindication to steroids or other active principles or excipients of the mouthwash

Where it is running

• University of California, Los Angeles — Los Angeles, California, United States
• Johns Hopkins Sibley Memorial Hospital — Washington D.C., District of Columbia, United States
• Winship Cancer Institute of Emory University — Atlanta, Georgia, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Tisch Cancer Institute, Icahn School of Medicine — New York, New York, United States
• Memorial Sloan-Kettering Cancer Center — New York, New York, United States
• Sarah Cannon Research Institute — Nashville, Tennessee, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• Next Oncology — San Antonio, Texas, United States
• START Oncology — San Antonio, Texas, United States
• Virginia Cancer Specialists — Fairfax, Virginia, United States
• Aichi Cancer Center — Nagoya, Aichi-ken, Japan
• The Cancer Institute Hospital of Japanese Foundation For Cancer Research — Koto-Ku, Tokyo, Japan
• Showa Medical University Hospital — Shinagawa-Ku, Tokyo, Japan
• National Cancer Center Hospital — Chūōku, Japan
• National Cancer Center Hospital East — Kashiwa, Japan

Full record on ClinicalTrials.gov

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