Clinical trial NCT03384940: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Neoplasm
Keywords: Oncology
HER2
Colorectal cancer
Antibody drug conjugate
ADC
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
name: AstraZeneca
First posted: 2017-12-28
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
measure: 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
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
Secondary outcomes:
measure: 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
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
measure: 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
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
measure: 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
timeFrame: 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
measure: Disease Control Rate (Confirmed and Unconfirmed) Following DS-8201a Treatment in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Advanced Colorectal Cancer
timeFrame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 18 months post-dose
measure: 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
timeFrame: Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months
measure: 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
timeFrame: Date of first dose to date of first objective documentation of PD or death (whichever occurs first), up to approximately 18 months
measure: 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
timeFrame: Time from the date of first dose to date of death from any cause, up to approximately 18 months
measure: 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
timeFrame: Time from the date of first dose to date of death from any cause, up to approximately 18 months
measure: Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
timeFrame: 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
measure: Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-11181a Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
timeFrame: 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
measure: Pharmacokinetic Parameter Time to Maximum Serum Concentration (Tmax) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
timeFrame: 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
measure: Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
timeFrame: 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
measure: 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
timeFrame: 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
measure: Treatment-Emergent Adverse Events (TEAEs) Reported By ≥20% Of Participants Following Treatment With DS-8201a in Participants With HER2-expressing Advanced Colorectal Cancer
timeFrame: From the date of signing the informed consent form up to 40 (+7) days after last dose, up to approximately 18 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Santa Monica
country: United States
facility: UCLA Health
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute
state: South Carolina
city: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center, University of Texas
state: Texas
city: Napoli
country: Italy
facility: Università degli studi della Campania L.Vanvitelli
state: Campania
city: Padova
country: Italy
facility: Oncology Institute Veneto IOV-IRCCS
state: Ferrara
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
state: Lombardo
city: Milan
country: Italy
facility: Fondazione IRCCS - Istituto Nazionale dei Tumori
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Ōsaka-sayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarre
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitari Clinic de Barcelona
city: Chelsea
country: United Kingdom
facility: Royal Marsden Institute (Chelsea)
state: London, England
city: Sutton
country: United Kingdom
facility: Royal Marsden Institute (Sutton)
state: Surrey, England
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
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.