Advanced Solid TumorsPhase 1NCT02564900

Study of DS-8201a in Subjects With Advanced Solid Malignant Tumors

A Phase 1 study testing DS-8201a (DP1), DS-8201a (DP2) and DS-8201a (DP) in people with Advanced Solid Tumors, run by Daiichi Sankyo Co., Ltd. at 14 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is an open-label, two-part, multicenter study to evaluate the safety and tolerability of DS-8201a in participants with advanced solid malignant tumors. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumors
What is being tested?: DS-8201a (DP1), DS-8201a (DP2) and DS-8201a (DP)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 292 participants
Where: 14 sitesin 2 countries
Study dates: 1 Sep 2015to 22 Dec 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Eastern Cooperative Oncology Group performance status( PS) of 0 or 1.
Left Ventricular Ejection Fraction (LVEF) ≥ 50%
Part 1:
Advanced/unresectable or metastatic breast cancer or gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Part 2a:
Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.

Show all 19Show fewer

Treated with ado-trastuzumab emtansine (T-DM1)
Part 2b:
Advanced gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Treated with trastuzumab
Part 2c:
Advanced breast cancer with HER2 low expression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Part 2d:
Satisfy at least one of the following criteria
Advanced/unresectable or metastatic solid malignant tumor with HER2 expression other than breast cancer and gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Advanced/unresectable or metastatic tumor with HER2 mutation that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Part 2e:
Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Treated with ado-trastuzumab emtansine (T-DM1) (patients with HER2 overexpression only)

Who cannot join

Has a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia.
Has a medical history of myocardial infarction or unstable angina.
Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females.
Has a medical history of clinically significant lung diseases

Trial locations and contacts

14 sites in 2 countries.

Country

City, postcode or hospital

14 sites in 2 countries

United States8 sites

Dana Farber Cancer Institute
Boston, Massachusetts, 02215
UC Health Clinical Trials Office
Cincinnati, Ohio, 45229
University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030-3721
Mayo Clinic
Jacksonville, Florida, 32224
University of Louisville
Louisville, Kentucky, 40202
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Sharp Memorial Hospital
San Diego, California, 92123
Washington University School of Medicine
St Louis, Missouri, 63110

Other trials in United States

Japan6 sites

Aichi Cancer Center Hospital
Aichi
National Cancer Center Hospital East
Chiba
Social Medical Corporation Hakuaikai Sagara Hospital
Kagoshima
Kindai University Hospital
Osaka
National Cancer Center Hospital
Tokyo
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Tokyo

Other trials in Japan

About this study

Official title: Phase 1, Two-Part, Multicenter, Non-randomized, Open-label, Multiple Dose First-In-Human Study of DS-8201A, in Subjects With Advanced Solid Malignant Tumors

This is an open-label, two-part, multicenter study to evaluate the safety and tolerability of DS-8201a in participants with advanced solid malignant tumors.

Conditions: Advanced Solid Tumors
Being tested: DS-8201a (DP1), DS-8201a (DP2), DS-8201a (DP)
Keywords: Advanced solid tumors, phase 1, oncology, HER2, Antibody drug conjugate (ADC)
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DS-8201a (DP1)Drug
DS-8201a to be administered via intravenous (IV) dose. DS-8201a (DP1) was used for the Dose Escalation phase and for Dose expansion Parts 2a, 2b, 2c, and 2d.
DS-8201a (DP2)Drug
DS-8201a is to be administered via intravenous (IV) dose. DS-8201a (DP2) was used only used for Dose Expansion Part 2e.
DS-8201a (DP)Drug
DS-8201a (DP) is to be administered via intravenous (IV) dose.

Study groups in NCT02564900
Study group	Role	What they receive
Part 1 Dose escalation	Experimental	Part 1 is a dose escalation to identify the Maximum Tolerated dose (MTD) or the recommended phase 2 dose of DS-8201a guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation with overdose control principal. Receives: Drug: DS-8201a (DP1); Drug: DS-8201a (DP)
Part 2 Dose expansion	Experimental	Part 2 is a dose expansion to examine the safety and efficacy of DS-8201a and it is consist of multiple cohorts: in subjects with trastuzumab emtansine (T-DM1)-treated HER2 overexpressing breast cancer (Part 2a); trastuzumab-treated HER2 overexpressing gastric or gastroesophageal junction adenocarcinoma (Part 2b); HER2 low expressing breast cancer (Part 2c), HER2 expressing other solid malignant tumor (Part 2d); HER2 expressing breast cancer (Japan only; Part 2e) Receives: Drug: DS-8201a (DP1); Drug: DS-8201a (DP2); Drug: DS-8201a (DP)

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Objective response rate (ORR) by independent central review was defined as the proportion of participants who achieve either complete response [CR] or partial response [PR] per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Measured: From 6 months postdose of last participant up to 3 years 5 months

Secondary outcomes (11)

Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Disease control rate (DCR) by independent central review was calculated as the proportion of participants demonstrating complete response (CR), partial response (PR), or stable disease (SD) for a minimum of 6 weeks (±1week) from the first dosing date. CR was defined as a disappearance of all target lesions, PR as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included 8 participants with salivary/submandibular/parotid gland, 2 breast with HER2-mutation, 2 endometrial, 2 esophageal, 2 Paget's disease, 1 cholangiocarcinoma, 1 extraskeletal myxoide chondrosarcoma, 1 gallbladder, 1 pancreatic, 1 small intestine, 1 uterine cervix, and 1 participant who received 5.4 mg/kg with HER2-low gastric/GEJ cancer.
Measured: From 6 months postdose of last participant up to 3 years 5 months
Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Best overall response by independent central review was defined as the proportion of participants who achieved either complete response [CR], partial response [PR], stable disease (SD), progressive disease (PD), or were non-evaluable (NE) as per RECIST v1.1. CR was defined as a disappearance of all target lesions, PR at least a 30% decrease in the sum of diameters of target lesions, and SD as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included 8 participants with salivary/submandibular/parotid gland, 2 breast with HER2-mutation, 2 endometrial, 2 esophageal, 2 Paget's disease, 1 cholangiocarcinoma, 1 extraskeletal myxoide chondrosarcoma, 1 gallbladder, 1 pancreatic, 1 small intestine, 1 uterine cervix, and 1 participant who received 5.4 mg/kg with HER2-low gastric/GEJ cancer.
Measured: From 6 months postdose of last participant up to 3 years 5 months
Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Duration of response (DoR) by independent central review was defined as the time between the date of the first complete response (CR) or partial response (PR) until the date of the first documentation of progressive disease (PD) or death due to any cause. CR was defined as a disappearance of all target lesions, PR as at least a 30% decrease in the sum of diameters of target lesions, and PD as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Measured: From 6 months postdose of last participant up to 3 years 5 months
Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Time to response (TTR) by independent central review was defined as the time interval between the date of registration until the date at which the criteria were first met for complete response (CR) or partial response (PR). Only participants who achieved CR or PR were included in the TTR analysis. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Measured: From 6 months postdose of last participant up to 3 years 5 months
Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Progression-free survival (PFS) by independent central review was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Measured: From 6 months postdose of last participant up to 3 years 5 months
Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Overall survival (OS) by independent central review was defined as the time interval from the date of enrollment to the date of death from any cause. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.
Measured: From 6 months postdose of last participant up to 3 years 5 months
Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose
The serum PK parameters of DS-8201a and its analytes for area under the concentration-versus-time curve from time 0 to the last quantifiable concentration as calculated by the linear-up log-down trapezoidal method (AUClast) and AUC from time 0 to infinity (AUCinf) elimination rate constant associated with the terminal phase were estimated using standard non-compartmental methods.
Measured: Post first dose up to Day 147
Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose
The serum PK parameters Maximum (peak) Observed serum concentration of DS-8201a and its analytes were estimated using standard non-compartmental method.
Measured: Post first dose up to Day 147
Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose
The serum PK parameters of Time of maximum plasma concentration (Tmax) for DS-8201a and its analytes were estimated using standard non-compartmental methods.
Measured: Post first dose up to Day 147
Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose
The serum PK parameters of Terminal elimination half-life for DS-8201a and its analytes was estimated using standard non-compartmental methods.
Measured: Post first dose up to Day 147
Overview of Treatment-emergent Adverse Events
Treatment-emergent adverse events were graded by Common Terminology Criteria for Adverse Events, v4.03.
Measured: Baseline up to 28 days after the last dose of study drug, up to 3 years 5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Sep 201522 Dec 2023

First posted1 Oct 2015 (estimated)
Study start1 Sep 2015
Primary completion1 Feb 2019
Study completion22 Dec 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Advanced Solid TumorsStudies 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: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 292 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02564900
Sponsor's protocol ID: DS8201-A-J101
Other IDs: 152978
Status last verified: Jan 2024
First submitted: 21 Sep 2015
Last updated: 22 Jan 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: De-identified individual participant data (IPD) 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

Tsurutani J, Iwata H, Krop I, Janne PA, Doi T, Takahashi S, Park H, Redfern C, Tamura K, Wise-Draper TM, Saito K, Sugihara M, Singh J, Jikoh T, Gallant G, Li BT. Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors. Cancer Discov. 2020 May;10(5):688-701. doi: 10.1158/2159-8290.CD-19-1014. Epub 2020 Mar 25.
PubMed 32213540
Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29.
PubMed 31047803
Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, Tsurutani J, Kadowaki S, Yamaguchi K, Iwasa S, Saito K, Fujisaki Y, Sugihara M, Shahidi J, Doi T. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):827-836. doi: 10.1016/S1470-2045(19)30088-9. Epub 2019 Apr 29.
PubMed 31047804
Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I; DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):610-621. doi: 10.1056/NEJMoa1914510. Epub 2019 Dec 11.
PubMed 31825192
Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, Shimizu C, Shimoi T, Kuboki Y, Matsubara N, Kitano A, Jikoh T, Lee C, Fujisaki Y, Ogitani Y, Yver A, Tamura K. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017 Nov;18(11):1512-1522. doi: 10.1016/S1470-2045(17)30604-6. Epub 2017 Oct 13.
PubMed 29037983
Takahashi S, Bando H, Kinoshita I, Modi S, Tsurutani J, Bang YJ, Sato Y, Nakatani S, Lee C, Sugihara M, Okuda Y, Iwata H. Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies. Jpn J Clin Oncol. 2024 Apr 6;54(4):434-443. doi: 10.1093/jjco/hyad181.
PubMed 38231777
Yin O, Iwata H, Lin CC, Tamura K, Watanabe J, Wada R, Kastrissios H, AbuTarif M, Garimella T, Lee C, Zhang L, Shahidi J, LaCreta F. Exposure-Response Relationships in Patients With HER2-Positive Metastatic Breast Cancer and Other Solid Tumors Treated With Trastuzumab Deruxtecan. Clin Pharmacol Ther. 2021 Oct;110(4):986-996. doi: 10.1002/cpt.2291. Epub 2021 Jun 10.
PubMed 33999422
Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, Krop IE, Lee C, Fujisaki Y, Sugihara M, Zhang L, Shahidi J, Takahashi S. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol. 2020 Jun 10;38(17):1887-1896. doi: 10.1200/JCO.19.02318. Epub 2020 Feb 14.
PubMed 32058843

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1, Two-Part, Multicenter, Non-randomized, Open-label, Multiple Dose First-In-Human Study of DS-8201A, in Subjects With Advanced Solid Malignant Tumors
ClinicalTrials.gov ID: NCT02564900
Acronym / sponsor ID: DS8201-A-J101
Conditions: Advanced Solid Tumors
Keywords: Advanced solid tumors, phase 1, oncology, HER2, Antibody drug conjugate (ADC)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 292 participants (actual)
Lead sponsor: Daiichi Sankyo Co., Ltd.Industry (pharma, biotech, devices)
Collaborators: Daiichi Sankyo, AstraZeneca
Study start: 1 Sep 2015 (actual)
Primary completion: 1 Feb 2019 (actual)
Study completion: 22 Dec 2023 (actual)
First posted: 1 Oct 2015 (estimated)
Results: Posted 23 Jun 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This is an open-label, two-part, multicenter study to evaluate the safety and tolerability of DS-8201a in participants with advanced solid malignant tumors.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Part 1 Dose escalation	Experimental	Drug: DS-8201a (DP1), Drug: DS-8201a (DP)Part 1 is a dose escalation to identify the Maximum Tolerated dose (MTD) or the recommended phase 2 dose of DS-8201a guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation with overdose control principal.
Part 2 Dose expansion	Experimental	Drug: DS-8201a (DP1), Drug: DS-8201a (DP2), Drug: DS-8201a (DP)Part 2 is a dose expansion to examine the safety and efficacy of DS-8201a and it is consist of multiple cohorts: in subjects with trastuzumab emtansine (T-DM1)-treated HER2 overexpressing breast cancer (Part 2a); trastuzumab-treated HER2 overexpressing gastric or gastroesophageal junction adenocarcinoma (Part 2b); HER2 low expressing breast cancer (Part 2c), HER2 expressing other solid malignant tumor (Part 2d); HER2 expressing breast cancer (Japan only; Part 2e)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

Eastern Cooperative Oncology Group performance status( PS) of 0 or 1.
Left Ventricular Ejection Fraction (LVEF) ≥ 50%
Advanced/unresectable or metastatic breast cancer or gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Advanced breast cancer with HER2 overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Treated with ado-trastuzumab emtansine (T-DM1)

Key exclusion criteria (4 listed)

Has a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia.
Has a medical history of myocardial infarction or unstable angina.
Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females.
Has a medical history of clinically significant lung diseases

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
DS-8201a (DP1)DS-8201a to be administered via intravenous (IV) dose. DS-8201a (DP1) was used for the Dose Escalation phase and for Dose expansion Parts 2a, 2b, 2c, and 2d.	Drug	Part 1 Dose escalation, Part 2 Dose expansion
DS-8201a (DP2)DS-8201a is to be administered via intravenous (IV) dose. DS-8201a (DP2) was used only used for Dose Expansion Part 2e.	Drug	Part 2 Dose expansion
DS-8201a (DP)DS-8201a (DP) is to be administered via intravenous (IV) dose.	Drug	Part 1 Dose escalation, Part 2 Dose expansion

Primary outcome

Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Objective response rate (ORR) by independent central review was defined as the proportion of participants who achieve either complete response [CR] or partial response [PR] per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer.

11 secondary outcomes

Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)
Time frame: From 6 months postdose of last participant up to 3 years 5 months
Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose
Time frame: Post first dose up to Day 147
Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose
Time frame: Post first dose up to Day 147
Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose
Time frame: Post first dose up to Day 147
Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose
Time frame: Post first dose up to Day 147
Overview of Treatment-emergent Adverse Events
Time frame: Baseline up to 28 days after the last dose of study drug, up to 3 years 5 months

Results and safety

Results posted to the registry on 23 Jun 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Escalation: Cohort 1, 0.8 mg/kg	3	0
Dose Escalation: Cohort 2, 1.6 mg/kg	3	0
Dose Escalation: Cohort 3, 3.2 mg/kg	3	0
Dose Escalation: Cohort 4, 5.4 mg/kg	6	0
Dose Escalation: Cohort 5, 6.4 mg/kg	6	0
Dose Escalation: Cohort 6, 8.0 mg/kg	6	0
Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg	0	0
Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg	0	0
Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg	0	0
Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg	0	0
Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg	0	0
Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg	0	0
Dose Expansion: HER2-expressing NSCLC Tumors	0	0
Dose Expansion: HER2-expressing Colorectal Tumors	0	0
Dose Expansion: HER2-expressing Other Solid Tumors	0	0

Primary outcome: Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)

Time frame: From 6 months postdose of last participant up to 3 years 5 months. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Dose Escalation: Cohort 1, 0.8 mg/kg n = 3	Dose Escalation: Cohort 2, 1.6 mg/kg n = 3	Dose Escalation: Cohort 3, 3.2 mg/kg n = 3	Dose Escalation: Cohort 4, 5.4 mg/kg n = 6	Dose Escalation: Cohort 5, 6.4 mg/kg n = 6	Dose Escalation: Cohort 6, 8.0 mg/kg n = 6	Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg n = 51	Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg n = 67	Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg n = 21	Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg n = 33	Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg n = 19	Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg n = 25	Dose Expansion: HER2-expressing NSCLC Tumors n = 18	Dose Expansion: HER2-expressing Colorectal Tumors n = 20	Dose Expansion: HER2-expressing Other Solid Tumors n = 23
Value	0 (0 to 70.8)	33.3 (0.8 to 90.6)	0 (0 to 70.8)	83.3 (35.9 to 99.6)	33.3 (4.3 to 77.7)	50.0 (11.8 to 88.2)	51.0 (36.6 to 65.2)	53.7 (41.1 to 66.0)	33.3 (14.6 to 57.0)	39.4 (22.9 to 57.9)	26.3 (9.1 to 51.2)	32.0 (14.9 to 53.5)	55.6 (30.8 to 78.5)	5.0 (0.1 to 24.9)	30.4 (13.2 to 52.9)

Population analysed: ORR was assessed among participants in the Intent-to-Treat Analysis Set.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse event (TEAE) data were collected from baseline up to 28 days after the last dose of study drug, up to 3 years 5 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose Escalation: Cohort 1, 0.8 mg/kg	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Dose Escalation: Cohort 2, 1.6 mg/kg	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Dose Escalation: Cohort 3, 3.2 mg/kg	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Dose Escalation: Cohort 4, 5.4 mg/kg	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6
Dose Escalation: Cohort 5, 6.4 mg/kg	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6
Dose Escalation: Cohort 6, 8.0 mg/kg	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6
Dose Expansion: HER2-positive Breast Cancer, 5.4 mg/kg	11 of 50 (22%)	50 of 50 (100%)	3 of 50
Dose Expansion: HER2-positive Breast Cancer, 6.4 mg/kg	17 of 66 (25.8%)	66 of 66 (100%)	1 of 66
Dose Expansion: HER2-low Expressing Breast Cancer, 5.4 mg/kg	3 of 21 (14.3%)	20 of 21 (95.2%)	0 of 21
Dose Expansion: HER2-low Expressing Breast Cancer, 6.4 mg/kg	12 of 33 (36.4%)	33 of 33 (100%)	0 of 33
Dose Expansion: HER2-overexpressing Gastric or GEJ, 5.4 mg/kg	4 of 19 (21.1%)	19 of 19 (100%)	1 of 19
Dose Expansion: HER2-overexpressing Gastric or GEJ, 6.4 mg/kg	7 of 25 (28%)	25 of 25 (100%)	1 of 25
Dose Expansion: HER2-expressing Other Solid Tumors	18 of 59 (30.5%)	59 of 59 (100%)	5 of 59

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 32213540Tsurutani J, Iwata H, Krop I, Janne PA, Doi T, Takahashi S, Park H, Redfern C, Tamura K, Wise-Draper TM, Saito K, Sugihara M, Singh J, Jikoh T, Gallant G, Li BT. Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors. Cancer Discov. 2020 May;10(5):688-701. doi: 10.1158/2159-8290.CD-19-1014. Epub 2020 Mar 25.
Results publication: PubMed 31047803Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29.
Results publication: PubMed 31047804Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, Tsurutani J, Kadowaki S, Yamaguchi K, Iwasa S, Saito K, Fujisaki Y, Sugihara M, Shahidi J, Doi T. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):827-836. doi: 10.1016/S1470-2045(19)30088-9. Epub 2019 Apr 29.
Results publication: PubMed 31825192Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I; DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):610-621. doi: 10.1056/NEJMoa1914510. Epub 2019 Dec 11.
Results publication: PubMed 29037983Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, Shimizu C, Shimoi T, Kuboki Y, Matsubara N, Kitano A, Jikoh T, Lee C, Fujisaki Y, Ogitani Y, Yver A, Tamura K. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017 Nov;18(11):1512-1522. doi: 10.1016/S1470-2045(17)30604-6. Epub 2017 Oct 13.
Derived from this study: PubMed 38231777Takahashi S, Bando H, Kinoshita I, Modi S, Tsurutani J, Bang YJ, Sato Y, Nakatani S, Lee C, Sugihara M, Okuda Y, Iwata H. Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies. Jpn J Clin Oncol. 2024 Apr 6;54(4):434-443. doi: 10.1093/jjco/hyad181.
Derived from this study: PubMed 33999422Yin O, Iwata H, Lin CC, Tamura K, Watanabe J, Wada R, Kastrissios H, AbuTarif M, Garimella T, Lee C, Zhang L, Shahidi J, LaCreta F. Exposure-Response Relationships in Patients With HER2-Positive Metastatic Breast Cancer and Other Solid Tumors Treated With Trastuzumab Deruxtecan. Clin Pharmacol Ther. 2021 Oct;110(4):986-996. doi: 10.1002/cpt.2291. Epub 2021 Jun 10.
Derived from this study: PubMed 32058843Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, Krop IE, Lee C, Fujisaki Y, Sugihara M, Zhang L, Shahidi J, Takahashi S. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol. 2020 Jun 10;38(17):1887-1896. doi: 10.1200/JCO.19.02318. Epub 2020 Feb 14.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) 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 Clinical Leader study director

Daiichi Sankyo

14 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 DS-8201a (DP1), DS-8201a (DP2) and DS-8201a (DP) in people with Advanced Solid Tumors, run by Daiichi Sankyo Co., Ltd. at 14 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 19 inclusion and 4 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: finished, as of the sponsor's last update on 22 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 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?

Yes. Results are posted in the registry (first posted 23 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (ORR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases) (time frame: From 6 months postdose of last participant up to 3 years 5 months). 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 NCT02564900, which also lists 8 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 22 Jan 2024; AzTrials last refreshed its copy on 30 Oct 2026.