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

Daiichi Sankyo Co., Ltd.86 enrolled

Overview

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

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Colorectal Neoplasm

Interventions

DS-8201aDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (25)

City of Hope Medical Center

Outcomes

Primary Outcomes

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.

Time frame: 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.

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

Secondary Outcomes

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.

Data from ClinicalTrials.gov

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Duarte, California, United States

University of Southern California

Los Angeles, California, United States

UCLA Health

Santa Monica, California, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Greenville Health System Cancer Institute

Greenville, South Carolina, United States

West Cancer Center

Germantown, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

MD Anderson Cancer Center, University of Texas

Houston, Texas, United States

Università degli studi della Campania L.Vanvitelli

Napoli, Campania, Italy

...and 15 more locations

Time frame: 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.

Time frame: 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.

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

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).

Time frame: 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

Time frame: 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.

Time frame: 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 frame: 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 frame: 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.

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

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.

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