NCT02564900 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2024-01-22

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

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

→

outcome · POSTED

Disease Control Rate (DCR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)

→

outcome · POSTED

Best Overall Response Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Escalation and Dose Expansion Phases)

→

outcome · POSTED

Duration of Response (DoR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)

→

outcome · POSTED

Time to Response (TTR) Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)

→

outcome · POSTED

Progression-free Survival Following Treatment With DS-8201a in Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)

→

outcome · POSTED

Overall Survival Among Participants With Advanced Solid Malignant Tumors (Dose Expansion Phases)

→

outcome · POSTED

Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum DS-8201a Following First Dose

→

outcome · POSTED

Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose

→

outcome · POSTED

Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose

→

outcome · POSTED

Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose

→

outcome · POSTED

Overview of Treatment-emergent Adverse Events

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: * 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. * 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 1. 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. 2. 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) Exclusion Criteria: * 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: DS-8201a (DP1)
Drug: DS-8201a (DP)
label
Part 1 Dose escalation
type
EXPERIMENTAL
description
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)
intervention Names
Drug: DS-8201a (DP1)
Drug: DS-8201a (DP2)
Drug: DS-8201a (DP)
label
Part 2 Dose expansion
type
EXPERIMENTAL

interventions

arm Group Labels
Part 1 Dose escalation
Part 2 Dose expansion
description
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.
name
DS-8201a (DP1)
type
DRUG
arm Group Labels
Part 2 Dose expansion
description
DS-8201a is to be administered via intravenous (IV) dose. DS-8201a (DP2) was used only used for Dose Expansion Part 2e.
name
DS-8201a (DP2)
type
DRUG
arm Group Labels
Part 1 Dose escalation
Part 2 Dose expansion
description
DS-8201a (DP) is to be administered via intravenous (IV) dose.
name
DS-8201a (DP)
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 292
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
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

secondary Outcomes

description
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.
measure
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
description
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.
measure
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
description
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.
measure
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
description
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.
measure
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
description
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.
measure
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
description
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.
measure
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
description
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.
measure
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
description
The serum PK parameters Maximum (peak) Observed serum concentration of DS-8201a and its analytes were estimated using standard non-compartmental method.
measure
Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose
time Frame
Post first dose up to Day 147
description
The serum PK parameters of Time of maximum plasma concentration (Tmax) for DS-8201a and its analytes were estimated using standard non-compartmental methods.
measure
Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose
time Frame
Post first dose up to Day 147
description
The serum PK parameters of Terminal elimination half-life for DS-8201a and its analytes was estimated using standard non-compartmental methods.
measure
Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose
time Frame
Post first dose up to Day 147
description
Treatment-emergent adverse events were graded by Common Terminology Criteria for Adverse Events, v4.03.
measure
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

Full study description

brief 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.

Source references

references

citation
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.
pmid
32213540
type
RESULT
citation
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.
pmid
31047803
type
RESULT
citation
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.
pmid
31047804
type
RESULT
citation
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.
pmid
31825192
type
RESULT
citation
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.
pmid
29037983
type
RESULT
citation
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.
pmid
38231777
type
DERIVED
citation
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.
pmid
33999422
type
DERIVED
citation
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.
pmid
32058843
type
DERIVED