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

NCT03401385 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: DS1062-A-J101173812
• Study Type: interventional
• Target: 890
• Locations: 2 countries
• Sites: 18

Brief Summary

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.

Conditions

Hormone Receptor Positive Breast Cancer; Triple Negative Breast Cancer; Non-small Cell Lung Cancer

Keywords

Hormone Receptor Positive Breast Cancer; Triple Negative Breast Cancer; Non-small Cell Lung Cancer; Other solid tumors

Outcome Measures

Primary Outcomes (3)

• Number of participants with dose-limiting toxicities

  Dose-limiting toxicities are defined as side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.

  Within 8 cycles (each cycle is 21 days)

• Number of participants with adverse events (AEs)

  When all participants have either discontinued the study or the last participant enrolled in the study has completed at least 6 months of follow up (approximately 4 years)

• Number of participants with Grade >/= 2 oral mucositis/stomatitis in Sub-Study

  At 8 weeks

Secondary Outcomes (5)

• Maximum concentration (Cmax)

  Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)

• Time at which Cmax is reached (Tmax)

  Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)

• Area under the drug concentration-time curve (AUC) to the last observable concentration (AUClast)

  Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)

• AUC during the dosing period (AUCtau)

  Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)

• Minimum observed concentration (Ctrough)

  Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)

Study Arms (2)

Dose Escalation - All Participants

EXPERIMENTAL

All participants enrolled in the dose escalation part

Drug: Datopotamab Deruxtecan (Dato-DXd)

Dose Expansion - All Participants

EXPERIMENTAL

All participants enrolled in the dose expansion part

Drug: Datopotamab Deruxtecan (Dato-DXd); Drug: Steroid Containing Mouthwash; Other: Non-Steroid Containing Mouthwash

Interventions

Datopotamab Deruxtecan (Dato-DXd) DRUG

A total anti-TROP2 antibody and MAAA-1181a

Also known as: DS1062a, Study treatment

Dose Escalation - All Participants; Dose Expansion - All Participants

Steroid Containing Mouthwash DRUG

A mouthwash containing a steroid ingredient administered in sub-study

Dose Expansion - All Participants

Non-Steroid Containing Mouthwash OTHER

A mouthwash containing a non-steroid ingredient administered in sub-study

Dose Expansion - All Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Participants:
• Has relapsed or progressed following local standard treatments or for which no standard treatment is available.
• 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.
• \- Has a pathologically documented unresectable advanced NSCLC disease not amenable to curative therapy.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead
• Daiichi Sankyo: collaborator
• AstraZeneca: collaborator

Study Sites (18)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Johns Hopkins Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Tisch Cancer Institute, Icahn School of Medicine

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37205, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Next Oncology

San Antonio, Texas, 78229, United States

Location

START Oncology

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

Location

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Koto-Ku, Tokyo, 135-8550, Japan

Location

Showa Medical University Hospital

Shinagawa-Ku, Tokyo, 142-0064, Japan

Location

National Cancer Center Hospital

Chūōku, 104-0045, Japan

Location

National Cancer Center Hospital East

Kashiwa, 277-8577, Japan

Location

Related Publications (3)

• Bardia A, Krop IE, Kogawa T, Juric D, Tolcher AW, Hamilton EP, Mukohara T, Lisberg A, Shimizu T, Spira AI, Tsurutani J, Damodaran S, Papadopoulos KP, Greenberg J, Kobayashi F, Zebger-Gong H, Wong R, Kawasaki Y, Nakamura T, Meric-Bernstam F. Datopotamab Deruxtecan in Advanced or Metastatic HR+/HER2- and Triple-Negative Breast Cancer: Results From the Phase I TROPION-PanTumor01 Study. J Clin Oncol. 2024 Jul 1;42(19):2281-2294. doi: 10.1200/JCO.23.01909. Epub 2024 Apr 23.

  PMID: 38652877 DERIVED

• Heist RS, Sands J, Bardia A, Shimizu T, Lisberg A, Krop I, Yamamoto N, Kogawa T, Al-Hashimi S, Fung SSM, Galor A, Pisetzky F, Basak P, Lau C, Meric-Bernstam F. Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan. Cancer Treat Rev. 2024 Apr;125:102720. doi: 10.1016/j.ctrv.2024.102720. Epub 2024 Mar 11.

  PMID: 38502995 DERIVED

• Shimizu T, Sands J, Yoh K, Spira A, Garon EB, Kitazono S, Johnson ML, Meric-Bernstam F, Tolcher AW, Yamamoto N, Greenberg J, Kawasaki Y, Zebger-Gong H, Kobayashi F, Phillips P, Lisberg AE, Heist RS. First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01. J Clin Oncol. 2023 Oct 10;41(29):4678-4687. doi: 10.1200/JCO.23.00059. Epub 2023 Jun 16.

  PMID: 37327461 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Global Team Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single group, but in two study parts, therefore two sequential arms are identified

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 17, 2018
• Study Start: January 31, 2018
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (13); JP (5)