DS-8201a in Human Epidermal Growth Factor Receptor2 (HER2)-Expressing Colorectal Cancer (DESTINY-CRC01)

NCT03384940 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: DS8201-A-J2032017-003466-28173808DESTINY-C01
• Study Type: interventional
• Target: 86
• Locations: 5 countries
• Sites: 25

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.

Conditions

Colorectal Neoplasm

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Best Objective Response Based on Independent Central Review (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer

  Best objective response was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, CR was defined as a disappearance of all target lesions, PR was defined 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.

  Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose

• Number of Participants With Objective Response Rate Based on Independent Central Review (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer

  Objective response rate (defined as CR+PR) was reported based on independent central review. As per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, 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.

  Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose

Secondary Outcomes (14)

• Number of Participants With Best Objective Response Based on Investigator (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer

  Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose

• Number of Participants With Objective Response Rate Based on Investigator (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer

  Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose

• Duration of Response (Confirmed and Unconfirmed) Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer

  Date of first documentation of objective response (CR or PR) up to date of first documentation of PD, up to approximately 18 months post-dose

• Disease Control Rate (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer

  Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose

• Progression-Free Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer

  Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months

Study Arms (3)

DS-8201a Cohort A

EXPERIMENTAL

Cohort A is comprised of participants with HER2-positive (IHC 3+ or IHC 2+/ISH +) who will receive DS-8201a once every 3 weeks

Drug: DS-8201a

DS-8201a Cohort B

EXPERIMENTAL

Cohort B is comprised of participants with HER2 IHC 2+/ISH - who will receive DS-8201a once every 3 weeks

Drug: DS-8201a

DS-8201a Cohort C

EXPERIMENTAL

Cohort C is comprised of participants with HER2 IHC 1+ who will receive DS-8201a once every 3 weeks

Drug: DS-8201a

Interventions

DS-8201a DRUG

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

Also known as: Trastuzumab deruxtecan

DS-8201a Cohort A; DS-8201a Cohort B; DS-8201a Cohort C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead
• Daiichi Sankyo: collaborator
• AstraZeneca: collaborator

Study Sites (25)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of Southern California

Los Angeles, California, 90089, United States

Location

UCLA Health

Santa Monica, California, 90404, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224-1865, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Greenville Health System Cancer Institute

Greenville, South Carolina, 29605-4255, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MD Anderson Cancer Center, University of Texas

Houston, Texas, 77030-4000, United States

Location

Università degli studi della Campania L.Vanvitelli

Napoli, Campania, 80131, Italy

Location

Oncology Institute Veneto IOV-IRCCS

Padua, Ferrara, 35128, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Lombardo, 20162, Italy

Location

Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, 791-0280, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Kindai University Hospital

Ōsaka-sayama, Osaka, 589-8511, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-Ku, Tokyo, 135-8550, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitari Clinic de Barcelona

Barcelona, 08036, Spain

Location

Royal Marsden Institute (Chelsea)

Chelsea, London, England, SM2 5PT, United Kingdom

Location

Royal Marsden Institute (Sutton)

Sutton, Surrey, England, SW3 6JJ, United Kingdom

Location

Related Publications (3)

• Siena S, Raghav K, Masuishi T, Yamaguchi K, Nishina T, Elez E, Rodriguez J, Chau I, Di Bartolomeo M, Kawakami H, Suto F, Koga M, Inaki K, Kuwahara Y, Takehara I, Barrios D, Kobayashi K, Grothey A, Yoshino T. HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01. Nat Commun. 2024 Nov 25;15(1):10213. doi: 10.1038/s41467-024-53223-3.

  PMID: 39587050 DERIVED

• Yoshino T, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Wainberg Z, Elez E, Rodriguez J, Fakih M, Ciardiello F, Saxena K, Kobayashi K, Bako E, Okuda Y, Meinhardt G, Grothey A, Siena S; DESTINY-CRC01 investigators. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun. 2023 Jun 7;14(1):3332. doi: 10.1038/s41467-023-38032-4.

  PMID: 37286557 DERIVED

• Siena S, Di Bartolomeo M, Raghav K, Masuishi T, Loupakis F, Kawakami H, Yamaguchi K, Nishina T, Fakih M, Elez E, Rodriguez J, Ciardiello F, Komatsu Y, Esaki T, Chung K, Wainberg Z, Sartore-Bianchi A, Saxena K, Yamamoto E, Bako E, Okuda Y, Shahidi J, Grothey A, Yoshino T; DESTINY-CRC01 investigators. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):779-789. doi: 10.1016/S1470-2045(21)00086-3. Epub 2021 May 4.

  PMID: 33961795 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sanyko, Inc.

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2017
• First Posted: December 28, 2017
• Study Start: February 23, 2018
• Primary Completion: August 9, 2019
• Study Completion: November 10, 2020
• Last Updated: October 18, 2021
• Results First Posted: August 24, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

US (9); IT (4); GB (2); ES (3); JP (7)