Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02564900
Recruitment Status : Active, not recruiting
First Posted : October 1, 2015
Results First Posted : June 23, 2021
Last Update Posted : June 23, 2021
Sponsor:
Collaborators:
Daiichi Sankyo, Inc.
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: DS-8201a (FL-DP1) Drug: DS-8201a (FL-DP2) Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 292 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 2015
Actual Primary Completion Date : February 1, 2019
Estimated Study Completion Date : September 30, 2021

Arm Intervention/treatment
Experimental: Part 1 Dose escalation
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.
Drug: DS-8201a (FL-DP1)
DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (50 mg/2.5 mL) to be administered via intravenous (IV) dose. DS-8201a (FL-DP1) was used for the Dose Escalation phase and for Dose expansion Parts 2a, 2b, 2c, and 2d.

Experimental: Part 2 Dose expansion
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)
Drug: DS-8201a (FL-DP1)
DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (50 mg/2.5 mL) to be administered via intravenous (IV) dose. DS-8201a (FL-DP1) was used for the Dose Escalation phase and for Dose expansion Parts 2a, 2b, 2c, and 2d.

Drug: DS-8201a (FL-DP2)
DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered via intravenous (IV) dose. DS-8201a (FL-DP2) was used only used for Dose Expansion Part 2e.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    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.

  3. 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 ]
    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.

  4. 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 ]
    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.

  5. 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 ]
    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.

  6. 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 ]
    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.

  7. 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 ]
    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.

  8. Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum DS-8201a Following First Dose [ Time Frame: Post first dose up to Day 147 ]
    The serum PK parameters Maximum (peak) Observed serum concentration of DS-8201a and its analytes were estimated using standard non-compartmental method.

  9. Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum DS-8201a Following First Dose [ Time Frame: Post first dose up to Day 147 ]
    The serum PK parameters of Time of maximum plasma concentration (Tmax) for DS-8201a and its analytes were estimated using standard non-compartmental methods.

  10. Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum DS-8201a Following First Dose [ Time Frame: Post first dose up to Day 147 ]
    The serum PK parameters of Terminal elimination half-life for DS-8201a and its analytes was estimated using standard non-compartmental methods.

  11. 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 ]
    Treatment-emergent adverse events were graded by Common Terminology Criteria for Adverse Events, v4.03.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02564900


Locations
Layout table for location information
United States, California
Sharp Memorial Hospital
San Diego, California, United States, 92123
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
UC Health Clinical Trials Office
Cincinnati, Ohio, United States, 45229
United States, Texas
University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States, 77030-3721
Japan
Aichi Cancer Center Hospital
Aichi, Japan
National Cancer Center Hospital East
Chiba, Japan
Social Medical Corporation Hakuaikai Sagara Hospital
Kagoshima, Japan
Kindai University Hospital
Osaka, Japan
National Cancer Center Hospital
Tokyo, Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Tokyo, Japan
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
Daiichi Sankyo, Inc.
AstraZeneca
Investigators
Layout table for investigator information
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Additional Information:
Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT02564900    
Other Study ID Numbers: DS8201-A-J101
152978 ( Registry Identifier: JAPIC CTI )
First Posted: October 1, 2015    Key Record Dates
Results First Posted: June 23, 2021
Last Update Posted: June 23, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):
Advanced solid tumors
phase 1
oncology
HER2
Antibody drug conjugate (ADC)
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Camptothecin
Immunoconjugates
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs