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

A Phase 2, Multicenter, Open-label Study of DS-8201a in Subjects With HER2-expressing Advanced Colorectal Cancer

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

Study Overview

• Status: Completed
• Conditions: Colorectal Neoplasm
• Intervention / Treatment: Drug: DS-8201a

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 Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS - Istituto Nazionale dei Tumori
  • Campania
    • Napoli, Campania, Italy, 80131
      • Università degli studi della Campania L.Vanvitelli
  • Ferrara
    • Padova, Ferrara, Italy, 35128
      • Oncology Institute Veneto IOV-IRCCS
  • Lombardo
    • Milano, Lombardo, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda
• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Osaka
    • Ōsaka-sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
  • Tokyo
    • Koto-Ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Universitari Clínic de Barcelona
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
• United Kingdom
  • London, England
    • Chelsea, London, England, United Kingdom, SM2 5PT
      • Royal Marsden Institute (Chelsea)
  • Surrey, England
    • Sutton, Surrey, England, United Kingdom, SW3 6JJ
      • Royal Marsden Institute (Sutton)
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Los Angeles, California, United States, 90089
      • University of Southern California
    • Santa Monica, California, United States, 90404
      • UCLA Health
  • Florida
    • Jacksonville, Florida, United States, 32224-1865
      • Mayo Clinic Jacksonville
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • South Carolina
    • Greenville, South Carolina, United States, 29605-4255
      • Greenville Health System Cancer Institute
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Cancer Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4000
      • MD Anderson Cancer Center, University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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	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 Names: Trastuzumab deruxtecan
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	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 Names: Trastuzumab deruxtecan
Experimental: DS-8201a Cohort C; Cohort C is comprised of participants with HER2 IHC 1+ who will receive DS-8201a once every 3 weeks	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 Names: Trastuzumab deruxtecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Best objective response was reported based on investigator. 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 Investigator (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 investigator. 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
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	Duration of response (DoR) is defined as the time from the date of the first documentation of an objective response (CR[disappearance of all target lesions] or PR [at least a 30% decrease in the sum of diameters of target lesions]) to the date of the first documentation of PD (at least a 20% increase in the sum of diameters of target lesions). Duration of response was measured for responding participants (CR or PR) only. Month was calculated as (duration of response days × 12)/365.25 for duration of response and calculated as (time to response days × 12)/365.25 for time to response.	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	Disease control rate (DCR) was defined as the proportion of participants who achieved a best overall response of CR + PR + SD based on independent central review and investigator assessment. As per RECIST v1.1, 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
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	Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.	Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months
Progression-Free Survival at Various Time Points Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer	Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) via independent radiologic facility review or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.Point estimates at 3, 6, 9, and 12 months are based on Kaplan-Meier estimate. CI is computed using the Brookmeyer-Crowley method. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported.	Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months
Overall Survival Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer	Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.	Time from the date of first dose to date of death from any cause, up to approximately 18 months
Overall Survival at Various Time Points Based on Independent Central Review Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer	Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause. The point estimate percentage (95% confidence interval) at 3, 6, 9, and 12 months is being reported.	Time from the date of first dose to date of death from any cause, up to approximately 18 months
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer	Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.	Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-11181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer	Maximum serum concentration (Cmax) of MAAA-1181a was assessed.	Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Pharmacokinetic Parameter Time to Maximum Serum Concentration (Tmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer	Time to maximum serum concentration (Tmax) of DS-8201a, total anti-HER2 antibody, and MAAA-1181a was assessed.	Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer	Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of DS-8201a and total anti-HER2 antibody were assessed.	Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) of MAAA-1181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer	Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of MAAA-1181a were assessed.	Cycle 1: Day 1, before infusion (BI), end of infusion (EOI); Day 8; Day 15; Cycle 2: Day 1, BI and EOI; Cycle 3: Day 1, BI, EOI, 4 hours after start of drug, and 7 hours after start of drug; Cycles 4 and 6: Day 1, BI and EOI
Treatment-Emergent Adverse Events (TEAEs) Reported By ≥20% Of Participants Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer	A treatment-emergent adverse event (TEAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TEAEs were graded using National Cancer Institute (NCI)-CTCAE version 4.03.	From the date of signing the informed consent form up to 40 (+7) days after last dose, up to approximately 18 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborators: AstraZeneca; Daiichi Sankyo, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2018
• Primary Completion (Actual): August 9, 2019
• Study Completion (Actual): November 10, 2020

Study Registration Dates

• First Submitted: December 20, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 28, 2017

Study Record Updates

• Last Update Posted (Actual): October 18, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Colorectal cancer; HER2; Oncology; ADC; Antibody drug conjugate
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: DS8201-A-J203; 2017-003466-28 (EudraCT Number); 173808 (Registry Identifier: JAPIC CTI); DESTINY-C01 (Other Identifier: Daiichi Sankyo and AstraZeneca)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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/
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No