DS-8201a in Human Epidermal Growth Factor Receptor2 (HER2)-Expressing Colorectal Cancer

• Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborator: Daiichi Sankyo, Inc.
• Information provided by (Responsible Party): Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Study Description

Brief Summary:

The main objective of this study is to test the safety and effectiveness of DS-8201a for participants with HER2-expressing advanced colorectal cancer.

Condition or disease	Intervention/treatment	Phase
Colorectal Neoplasm	Drug: DS-8201a	Phase 2

Detailed Description:

At study start, only Cohort A is active.

If, and when, Cohort B and C become active depends on the assessment of benefit and risk observed in the program.

The sponsor will inform the investigators if, and when, Cohort B and C are active.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	90 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Colorectal Cancer
Actual Study Start Date :	February 23, 2018
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	June 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: DS-8201a Cohort A; Cohort A is comprised of participants with HER2-positive (IHC 3+ or IHC 2+/ISH +) who will receive DS-8201a once every 3 weeks Enrollment to this cohort was closed and this cohort is active until study completion.	Drug: DS-8201a; DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration; Other Name: Experimental product
Experimental: DS-8201a Cohort B; Cohort B is comprised of participants with HER2 IHC 2+/ISH - who will receive DS-8201a once every 3 weeks This cohort is active.	Drug: DS-8201a; DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration; Other Name: Experimental product
Experimental: DS-8201a Cohort C; Cohort C is comprised of participants with HER2 IHC 1+ who will receive DS-8201a once every 3 weeks This cohort is active.	Drug: DS-8201a; DS-8201a is comprised of an antibody component conjoined to a drug component in a lyophilized powder, which is made into solution for intravenous administration; Other Name: Experimental product

Outcome Measures

Primary Outcome Measures :

1. Objective response rate (ORR) per imaging assessment [ Time Frame: from Cycle 1 Day 1 through disease progression (within 18 months) ]
   Percentage of participants with objective response per independent central imaging facility review based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 in Cohort A

Secondary Outcome Measures :

1. Progression-free survival [ Time Frame: within 18 months ]
   Percentage of participants still alive without the disease getting worse
2. Overall survival (OS) [ Time Frame: at 18 months ]
   Percentage of participants still alive
3. Duration of response [ Time Frame: within 18 months ]
   Length of time response continued
4. Disease control rate (DCR) [ Time Frame: within 18 months ]
   Percentage of participants with controlled disease
5. ORR assessed by the investigator based on RECIST version 1.1 [ Time Frame: within 18 months ]
   Percentage of participants with objective response as assessed by the investigator, based on RECIST version 1.1
6. Maximum serum/plasma concentration (Cmax) [ Time Frame: within 21 days ]
   Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a
7. Time to Cmax (Tmax) [ Time Frame: within 21 days ]
   Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a
8. Area under the concentration-time curve (AUC) from dosing until the last quantifiable concentration (AUClast) [ Time Frame: within 21 days ]
   Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a
9. AUC from the time of dosing until day 21 (AUC0-21d) [ Time Frame: at Day 21 ]
   Categories: DS-8201a, total anti-HER2 antibody, and MAAA-1181a

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Has pathologically documented unresectable, recurrent, or metastatic colorectal adenocarcinoma (until sponsor's notification to the study sites, subject must be a RAS/BRAF wild-type cancer)
• Has received at least 2 prior regimens of standard treatment
• Has measurable disease assessed by the investigator based on RECIST version 1.1.
• Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1

Exclusion Criteria:

• Has a medical history of myocardial infarction within 6 months, symptomatic congestive heart failure
• Has a medical history of clinically significant lung disease
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy

Contacts and Locations

Contacts

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Contact: (Japanese sites only) Daiichi Sankyo Contact for Clinical Trial Information	+81-3-6225-1111(M-F 9-5 JST)	dsclinicaltrial@daiichisankyo.co.jp

Locations

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United States, California
City of Hope Medical Center	Recruiting
Duarte, California, United States, 91010
Contact: Principal Investigator 626-256-4673 mfakih@coh.org
University of Southern California	Recruiting
Los Angeles, California, United States, 90089
Contact: Principal Investigator 323-865-3967 LENZ@med.usc.edu
UCLA Health	Recruiting
Santa Monica, California, United States, 90404
Contact: Principal Investigator 310-829-5471 zwainberg@mednet.ucla.edu
United States, Michigan
Karmanos Cancer Institute	Recruiting
Detroit, Michigan, United States, 48201
Contact: Principal Investigator 313-576-8735 shieldsa@karmanos.org
United States, South Carolina
Greenville Health System Cancer Institute	Recruiting
Greenville, South Carolina, United States, 29605-4255
Contact: Principal Investigator 864-699-5700 kchung@ghs.org
United States, Tennessee
Vanderbilt University Medical Center	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Principal Investigator 615-343-4669 kristen.k.ciombor@vanderbilt.edu
United States, Texas
MD Anderson Cancer Center, University of Texas	Recruiting
Houston, Texas, United States, 77030-4000
Contact: Principal Investigator 713-792-6161 KPRaghav@mdanderson.org
Italy
Università degli studi della Campania L.Vanvitelli	Recruiting
Napoli, Campania, Italy, 80131
Contact: Principal Investigator +39 0815666760 fortunato.ciardiello@unicampania.it
Oncology Institute Veneto IOV-IRCCS	Recruiting
Padova, Ferrara, Italy, 35128
Contact: Principal Investigator +39 3289634053 fotios.loupakis@iov.veneto.it
ASST Grande Ospedale Metropolitano Niguarda	Recruiting
Milano, Lombardo, Italy, 20162
Contact: Principal Investigator +39 0264442291 salvatore.siena@unimi.it
Fondazione IRCCS - Istituto Nazionale dei Tumori	Recruiting
Milan, Italy, 20133
Contact: Principal Investigator +39 0223902882 maria.dibartolomeo@istitutotumori.mi.it
Japan
Aichi Cancer Center Hospital	Recruiting
Nagoya, Aichi, Japan, 464-8681
Contact: See Central Contact
National Cancer Center Hospital East	Recruiting
Kashiwa, Chiba, Japan, 277-8577
Contact: See Central Contact
National Hospital Organization Shikoku Cancer Center	Recruiting
Matsuyama, Ehime, Japan, 791-0280
Contact: See Central Contact
Hokkaido University Hospital	Recruiting
Sapporo, Hokkaido, Japan, 060-8648
Contact: See Central Contact
Kindai University Hospital	Recruiting
Ōsaka-sayama, Osaka, Japan, 589-8511
Contact: See Central Contact
The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Recruiting
Koto-Ku, Tokyo, Japan, 135-8550
Contact: See Central Contact
National Hospital Organization Kyushu Cancer Center	Recruiting
Fukuoka, Japan, 811-1395
Contact: See Central Contact
Spain
Clinica Universidad de Navarra	Recruiting
Pamplona, Navarre, Spain, 31008
Contact: Principal Investigator +34 948255400 jrodriguez@unav.es
Hospital Universitari Vall d'Hebron	Recruiting
Barcelona, Spain, 08035
Contact: Principal Investigator +34 932746085 meelez@vhio.net
Hospital Universitari Clinic de Barcelona	Recruiting
Barcelona, Spain, 08036
Contact: Principal Investigator +34 932275402 JMAUREL@clinic.cat
United Kingdom
Royal Marsden Institute (Chelsea)	Recruiting
Chelsea, London, England, United Kingdom, SM2 5PT
Contact: Principal Investigator +44 02086613582 Ian.Chau@rmh.nhs.uk
Royal Marsden Institute (Sutton)	Recruiting
Sutton, Surrey, England, United Kingdom, SW3 6JJ
Contact: Principal Investigator +44 02086613582 Ian.Chau@rmh.nhs.uk

Sponsors and Collaborators

Daiichi Sankyo Co., Ltd.

Daiichi Sankyo, Inc.

Investigators

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Study Director:	Global Clinical Leader	Daiichi Sankyo, Inc.

More Information

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Responsible Party:	Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier:	NCT03384940 History of Changes
Other Study ID Numbers:	DS8201-A-J203; 2017-003466-28 ( EudraCT Number ); 173808 ( Registry Identifier: JAPIC CTI )
First Posted:	December 28, 2017
Last Update Posted:	June 11, 2019
Last Verified:	June 2019
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/

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. ):

Oncology; HER2; Colorectal cancer; Antibody drug conjugate; ADC

Additional relevant MeSH terms:

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Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases	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