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

Primary Purpose

Colorectal Neoplasm

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

DS-8201a

About this trial

This is an interventional treatment trial for Colorectal Neoplasm focused on measuring Oncology, HER2, Colorectal cancer, Antibody drug conjugate, ADC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

City of Hope Medical Center
University of Southern California
UCLA Health
Mayo Clinic Jacksonville
Karmanos Cancer Institute
Greenville Health System Cancer Institute
West Cancer Center
Vanderbilt University Medical Center
MD Anderson Cancer Center, University of Texas
Università degli studi della Campania L.Vanvitelli
Oncology Institute Veneto IOV-IRCCS
ASST Grande Ospedale Metropolitano Niguarda
Fondazione IRCCS - Istituto Nazionale dei Tumori
Aichi Cancer Center Hospital
National Cancer Center Hospital East
National Hospital Organization Shikoku Cancer Center
Hokkaido University Hospital
Kindai University Hospital
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
National Hospital Organization Kyushu Cancer Center
Clinica Universidad de Navarra
Hospital Universitari Vall d'Hebron
Hospital Universitari Clinic de Barcelona
Royal Marsden Institute (Chelsea)
Royal Marsden Institute (Sutton)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

DS-8201a Cohort A

DS-8201a Cohort B

DS-8201a Cohort C

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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).

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT03384940

First Posted

December 20, 2017

Last Updated

September 21, 2021

Sponsor

Daiichi Sankyo Co., Ltd.

Collaborators

Daiichi Sankyo, Inc., AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT03384940

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Completed

Study Start Date

February 23, 2018 (Actual)

Primary Completion Date

August 9, 2019 (Actual)

Study Completion Date

November 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Daiichi Sankyo Co., Ltd.

Collaborators

Daiichi Sankyo, Inc., AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Neoplasm

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

86 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DS-8201a Cohort A

Arm Type

Experimental

Arm Description

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

Arm Title

DS-8201a Cohort B

Arm Type

Experimental

Arm Description

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

Arm Title

DS-8201a Cohort C

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

DS-8201a

Other Intervention Name(s)

Trastuzumab deruxtecan

Intervention Description

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

Primary Outcome Measure Information:

Title

Description

Time Frame

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

Title

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Description

Time Frame

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

Title

Description

Time Frame

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

Title

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

Description

Time Frame

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

Title

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

Description

Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.

Time Frame

Time from the date of first dose to date of death from any cause, up to approximately 18 months

Title

Description

Time Frame

Time from the date of first dose to date of death from any cause, up to approximately 18 months

Title

Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer

Description

Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.

Time Frame

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

Title

Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-11181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer

Description

Maximum serum concentration (Cmax) of MAAA-1181a was assessed.

Time Frame

Title

Pharmacokinetic Parameter Time to Maximum Serum Concentration (Tmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer

Description

Time to maximum serum concentration (Tmax) of DS-8201a, total anti-HER2 antibody, and MAAA-1181a was assessed.

Time Frame

Title

Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer

Description

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.

Time Frame

Title

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

Description

Area under the concentration-time curve (AUC) from dosing until 21 days (AUC21d) and the last quantifiable concentration (AUClast) of MAAA-1181a were assessed.

Time Frame

Title

Treatment-Emergent Adverse Events (TEAEs) Reported By ≥20% Of Participants Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer

Description

Time Frame

From the date of signing the informed consent form up to 40 (+7) days after last dose, up to approximately 18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Global Clinical Leader

Organizational Affiliation

Daiichi Sankyo, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

City of Hope Medical Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

University of Southern California

City

Los Angeles

State/Province

California

ZIP/Postal Code

90089

Country

United States

Facility Name

UCLA Health

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

Mayo Clinic Jacksonville

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32224-1865

Country

United States

Facility Name

Karmanos Cancer Institute

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Greenville Health System Cancer Institute

City

Greenville

State/Province

South Carolina

ZIP/Postal Code

29605-4255

Country

United States

Facility Name

West Cancer Center

City

Germantown

State/Province

Tennessee

ZIP/Postal Code

38138

Country

United States

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

MD Anderson Cancer Center, University of Texas

City

Houston

State/Province

Texas

ZIP/Postal Code

77030-4000

Country

United States

Facility Name

Università degli studi della Campania L.Vanvitelli

City

Napoli

State/Province

Campania

ZIP/Postal Code

80131

Country

Italy

Facility Name

Oncology Institute Veneto IOV-IRCCS

City

Padova

State/Province

Ferrara

ZIP/Postal Code

35128

Country

Italy

Facility Name

ASST Grande Ospedale Metropolitano Niguarda

City

Milano

State/Province

Lombardo

ZIP/Postal Code

20162

Country

Italy

Facility Name

Fondazione IRCCS - Istituto Nazionale dei Tumori

City

Milan

ZIP/Postal Code

20133

Country

Italy

Facility Name

Aichi Cancer Center Hospital

City

Nagoya

State/Province

Aichi

ZIP/Postal Code

464-8681

Country

Japan

Facility Name

National Cancer Center Hospital East

City

Kashiwa

State/Province

Chiba

ZIP/Postal Code

277-8577

Country

Japan

Facility Name

National Hospital Organization Shikoku Cancer Center

City

Matsuyama

State/Province

Ehime

ZIP/Postal Code

791-0280

Country

Japan

Facility Name

Hokkaido University Hospital

City

Sapporo

State/Province

Hokkaido

ZIP/Postal Code

060-8648

Country

Japan

Facility Name

Kindai University Hospital

City

Ōsaka-sayama

State/Province

Osaka

ZIP/Postal Code

589-8511

Country

Japan

Facility Name

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

City

Koto-Ku

State/Province

Tokyo

ZIP/Postal Code

135-8550

Country

Japan

Facility Name

National Hospital Organization Kyushu Cancer Center

City

Fukuoka

ZIP/Postal Code

811-1395

Country

Japan

Facility Name

Clinica Universidad de Navarra

City

Pamplona

State/Province

Navarre

ZIP/Postal Code

31008

Country

Spain

Facility Name

Hospital Universitari Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hospital Universitari Clinic de Barcelona

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Royal Marsden Institute (Chelsea)

City

Chelsea

State/Province

London, England

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

Facility Name

Royal Marsden Institute (Sutton)

City

Sutton

State/Province

Surrey, England

ZIP/Postal Code

SW3 6JJ

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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 URL

https://vivli.org/ourmember/daiichi-sankyo/

Citations:

PubMed Identifier

33961795

Citation

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.

Results Reference

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

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