Hormone Receptor Positive Breast CancerPhase 1NCT03401385
First-in-human Study of DS-1062a for Advanced Solid Tumors (TROPION-PanTumor01)
A Phase 1 study testing Datopotamab Deruxtecan (Dato-DXd), Steroid Containing Mouthwash and Non-Steroid Containing Mouthwash in people with Hormone Receptor Positive Breast Cancer and Triple Negative Breast Cancer, run by Daiichi Sankyo Co., Ltd. at 18 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hormone Receptor Positive Breast Cancer, Triple Negative Breast Cancer, Non-small Cell Lung Cancer
- What is being tested?
- Datopotamab Deruxtecan (Dato-DXd), Steroid Containing Mouthwash and Non-Steroid Containing Mouthwash
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 890 participants
- Where
- 18 sitesin 2 countries
- Study dates
- 31 Jan 2018to 1 Jan 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- Additional Inclusion Criteria for Small-cell lung cancer (SCLC) participants:
- 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 and/or irinotecan.
- Additional Inclusion Criteria for Endometrial cancer participants:
- Pathologically documented recurrent or persistent endometrial cancer that relapsed or progressed after any established and/or curative therapies, including at least 1 systemic therapy.
- Additional Inclusion Criteria for Pancreatic adenocarcinoma participants:
- 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.
- Additional Inclusion Criteria for HER2-negative gastroesophageal cancer participants:
- 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.
- 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.
- Additional Inclusion Criteria for Esophageal cancer participants:
- 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.
- Additional Inclusion Criteria for Head and neck squamous cell carcinoma (HNSCC) participants:
- 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.
- Additional Inclusion Criteria for participants with advanced-stage urothelial cancer:
- Pathologically documented unresectable, locally advanced or metastatic, urothelial 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 an ICI.
- Additional Inclusion Criteria for Colorectal cancer (CRC) participants:
- 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.
- Additional Inclusion Criteria for Platinum-resistant ovarian cancer participants:
- 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.
- Additional Inclusion Criteria for Platinum-sensitive ovarian cancer participants:
- 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 chemotherapy.
- Additional Inclusion Criteria for Cervical cancer participants:
- Pathologically documented unresectable or metastatic cervical cancer that relapsed or progressed after at least 1 prior line of systemic therapy.
- Additional Inclusion Criteria for Castration-resistant prostate cancer participants:
- Pathologically documented unresectable CRPC that:
- Is adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
- Is surgically or medically castrated, with testosterone levels of less than 50 nanograms per deciliter.
- Objective progression as determined by radiographic progression for participants with measurable disease after androgen deprivation.
- Has relapsed or progressed after at least 1 of the following: abiraterone, enzalutamide, apalutamide or darolutamide.
- Has at least 1 documented lesion on either a bone scan or a CT/MRI scan.
- CRPC subjects will be chemotherapy-naïve.
- Additional inclusion criteria for HR-positive HER2-low breast cancer subjects previously treated with T-DXd
- Pathologically documented unresectable or metastatic breast cancer that is:
- HER2-low, defined as IHC 1+ or IHC 2+ / ISH-negative as classified by ASCO-CAP.
- Positive for estrogen receptor and/or progesterone receptor
- Was previously treated with T-DXd in the advanced or metastatic setting
- Additional Inclusion Criteria for Sub-study:
- Is competent and able to comprehend, sign, and date both the main study and the oral mucositis/stomatitis addendum informed consent forms (ICFs) prior to the start of any sub-study procedure or assessment
- Is willing to comply with the procedures of the sub-study, including keeping a daily questionnaire on oral hygiene and oral mucositis/stomatitis-related symptoms
Who cannot join
- 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.
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- 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
Trial locations and contacts
18 sites in 2 countries.
18 sites in 2 countries
United States13 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Virginia Cancer Specialists
Fairfax, Virginia, 22031
MD Anderson Cancer Center
Houston, Texas, 77030
University of California, Los Angeles
Los Angeles, California, 90095
Sarah Cannon Research Institute
Nashville, Tennessee, 37205
Tisch Cancer Institute, Icahn School of Medicine
New York, New York, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Next Oncology
San Antonio, Texas, 78229
START Oncology
San Antonio, Texas, 78229
Johns Hopkins Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Japan5 sites
National Cancer Center Hospital
Chūōku, 104-0045
National Cancer Center Hospital East
Kashiwa, 277-8577
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Koto-Ku, Tokyo, 135-8550
Aichi Cancer Center
Nagoya, Aichi-ken, 464-8681
Showa Medical University Hospital
Shinagawa-Ku, Tokyo, 142-0064
About this study
Official title: Phase 1, Two-part, Multicenter, Open-label, Multiple Dose, First-in-human Study of DS-1062a in Subjects With Advanced Solid Tumors (TROPION-PanTumor01)
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:
Read more
- 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.
Read the detailed description
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, HR-positive HER2-low breast cancer, HER2-positive 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.
In the sub-study, the additional indications listed for Dose Expansion (except for head and neck cancer) may be evaluated.
- Conditions
- Hormone Receptor Positive Breast Cancer, Triple Negative Breast Cancer, Non-small Cell Lung Cancer
- Being tested
- Datopotamab Deruxtecan (Dato-DXd), Steroid Containing Mouthwash, Non-Steroid Containing Mouthwash
- Keywords
- Hormone Receptor Positive Breast Cancer, Triple Negative Breast Cancer, Non-small Cell Lung Cancer, Other solid tumors
- Medical subject headings
- Triple Negative Breast Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Datopotamab Deruxtecan (Dato-DXd)Drug
Also called DS1062a, Study treatment
A total anti-TROP2 antibody and MAAA-1181a
Steroid Containing MouthwashDrug
A mouthwash containing a steroid ingredient administered in sub-study
Non-Steroid Containing MouthwashOther
A mouthwash containing a non-steroid ingredient administered in sub-study
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation - All Participants | Experimental | All participants enrolled in the dose escalation part Receives: Drug: Datopotamab Deruxtecan (Dato-DXd) |
| Dose Expansion - All Participants | Experimental | All participants enrolled in the dose expansion part Receives: Drug: Datopotamab Deruxtecan (Dato-DXd); Drug: Steroid Containing Mouthwash; Other: Non-Steroid Containing Mouthwash |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 8 cycles (each cycle is 21 days)
Number of participants with adverse events (AEs)
Measured: 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
Measured: At 8 weeks
Secondary outcomes (5)
Maximum concentration (Cmax)
Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Measured: Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)
Time at which Cmax is reached (Tmax)
Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Measured: 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)
Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Measured: Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)
AUC during the dosing period (AUCtau)
Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Measured: Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)
Minimum observed concentration (Ctrough)
Categories: DS-1062a, total anti-TROP2 antibody, MAAA-1181a
Measured: Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start31 Jan 2018
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hormone Receptor Positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Single group, but in two study parts, therefore two sequential arms are identified
- Masking
- None (open label)
- Enrolment
- 890 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo, AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Global Team Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03401385
- Sponsor's protocol ID
- DS1062-A-J101
- Other IDs
- 173812
- Status last verified
- Aug 2026
- First submitted
- 9 Jan 2018
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Publications
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.
PubMed 38652877Heist 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.
PubMed 38502995Shimizu 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.
PubMed 37327461
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Two-part, Multicenter, Open-label, Multiple Dose, First-in-human Study of DS-1062a in Subjects With Advanced Solid Tumors (TROPION-PanTumor01)
- ClinicalTrials.gov ID
- NCT03401385
- Acronym / sponsor ID
- DS1062-A-J101
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 890 participants (estimated)
- Lead sponsor
- Daiichi Sankyo Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo, AstraZeneca
- Study start
- 31 Jan 2018 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 17 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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, HR-positive HER2-low breast cancer, HER2-positive 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.
In the sub-study, the additional indications listed for Dose Expansion (except for head and neck cancer) may be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Single group, but in two study parts, therefore two sequential arms are identified
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation - All Participants | Experimental | Drug: Datopotamab Deruxtecan (Dato-DXd)All participants enrolled in the dose escalation part |
| Dose Expansion - All Participants | Experimental | Drug: Datopotamab Deruxtecan (Dato-DXd), Drug: Steroid Containing Mouthwash, Other: Non-Steroid Containing MouthwashAll participants enrolled in the dose expansion part |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (70 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Datopotamab Deruxtecan (Dato-DXd)Also: DS1062a, Study treatmentA total anti-TROP2 antibody and MAAA-1181a | Drug | Dose Escalation - All Participants, Dose Expansion - All Participants |
| Steroid Containing MouthwashA mouthwash containing a steroid ingredient administered in sub-study | Drug | Dose Expansion - All Participants |
| Non-Steroid Containing MouthwashA mouthwash containing a non-steroid ingredient administered in sub-study | Other | Dose Expansion - All Participants |
Primary outcome
Number of participants with dose-limiting toxicities
Time frame: Within 8 cycles (each cycle is 21 days)
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.
Number of participants with adverse events (AEs)
Time frame: 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
Time frame: At 8 weeks
5 secondary outcomes
Maximum concentration (Cmax)
Time frame: Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)
Time at which Cmax is reached (Tmax)
Time frame: 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)
Time frame: Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)
AUC during the dosing period (AUCtau)
Time frame: Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)
Minimum observed concentration (Ctrough)
Time frame: Within 8 cycles (each cycle is 21 days for Q3W or 14 days for Q2W)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Derived from this study: PubMed 38652877Bardia 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.
- Derived from this study: PubMed 38502995Heist 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.
- Derived from this study: PubMed 37327461Shimizu 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.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Team Leader study director
Daiichi Sankyo
18 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Datopotamab Deruxtecan (Dato-DXd), Steroid Containing Mouthwash and Non-Steroid Containing Mouthwash in people with Hormone Receptor Positive Breast Cancer and Triple Negative Breast Cancer, run by Daiichi Sankyo Co., Ltd. at 18 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 70 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with dose-limiting toxicities (time frame: Within 8 cycles (each cycle is 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03401385, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.