Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer

Advanced Colorectal Cancer Clinical Trial

— DESTINY-CRC02  

Official title:

A Phase 2, Multicenter, Randomized, Study of Trastuzumab Deruxtecan in Participants With HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal Cancer (DESTINY-CRC02)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04744831
• Other study ID #: DS8201-A-U207
• Secondary ID: 2020-004782-39
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 5, 2021
• Est. completion date: July 1, 2024

Study information

• Verified date: March 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of Trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor 2 (HER2)-overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC).

Description:

This 2-stage study will evaluate participants with locally advanced, unresectable, or metastatic HER2-overexpressing colorectal cancer (CRC) (immunohistochemistry [IHC] 3+ or IHC 2+/ in situ hybridization [ISH]+) of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type and either rat sarcoma viral oncogenes homologue (RAS) wild-type or mutant tumor type, previously treated with standard therapy. In the first stage, participants will be randomized 1:1 with 2 doses of T-DXd. After Stage 1 enrollment is complete, all further eligible participants will be registered to T-DXd administered IV in Stage 2. Participants will receive the assigned dose of T-DXd until progression of disease or the participant meets one of the discontinuation criteria.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 122
• Est. completion date: July 1, 2024
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

KEY Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for

randomization/registration into the study:

1. Adults aged =20 years in Japan, Taiwan, and Korea, or those aged =18 years in other countries, at the time the Informed Consent Forms (ICFs) are signed.

2. Pathologically-documented, unresectable, recurrent, or metastatic colorectal adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status identified in primary or metastatic site.

3. The following therapies should be included in prior lines of therapy:

1. Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated

2. Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if clinically indicated

3. Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated

4. Anti-programmed death ligand 1 (PD-(L)-1) therapy, if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high, if clinically indicated

4. Confirmed human epidermal growth factor 2 (HER2)-overexpressing status assessed by central laboratory and defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ hybridization (ISH) +.

5. Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.

6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

7. Has left ventricular ejection fraction (LVEF) =50% within 28 days before randomization/registration. KEY Exclusion Criteria: Participants who meet any of the following criteria will be disqualified from entering the

study:

1. Medical history of myocardial infarction (MI) within 6 months before randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal (ULN) at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before randomization/registration to rule out MI.

2. Has a corrected QT interval corrected with Fridericia's formula (QTcF) prolongation to >470 msec (female participants) or >450 msec (male participants) based on the average of the Screening triplicate 12-lead electrocardiograms (ECGs).

3. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.

4. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the randomization/registration, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.).

5. Any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of Screening.

6. Prior pneumonectomy.

7. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiotherapy and randomization/registration.

8. Participants with leptomeningeal carcinomatosis.

9. Has known human immunodeficiency virus (HIV) infection.

10. Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days before study randomization/registration. Participants with past or resolved hepatitis B virus (HBV) infection are eligible if hepatitis B surface antigen (HBsAg) negative (-) and antibody to hepatitis B core antigen (anti-HBc) positive (+). Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).

11. Previous treatment with a DXd-containing antibody-drug conjugate (ADC).

Related Conditions & MeSH terms

• Advanced Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• DS-8201a 5.4 mg/kg Q3W
DS-8201a for injection will be administered intravenously (IV) at a dose of 5.4 mg/kg every 3 weeks (Q3W)
• DS-8201a 6.4 mg/kg Q3W
DS-8201a for injection will be administered intravenously (IV) at a dose of 6.4 mg/kg every 3 weeks (Q3W)

Locations

Country	Name	City	State
Australia	Flinders Medical Centre (FMC)	Bedford Park
Australia	Blacktown Hospital	Blacktown
Australia	Royal Brisbane & Women's Hospital	Brisbane
Australia	Monash Medical Centre	Clayton
Australia	Peter MacCallum Cancer Centre	Melbourne
Belgium	UCL St-Luc	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
France	Hopital Edouard Herriot	Lyon Cedex 03
France	ICM-Val d'Aurelle	MONTPELLIER Cedex 5
France	University Hospital of nantes	Nantes
France	Hopital St Antoine	Paris
France	Chu Toulouse	Toulouse
Italy	Asst Grande Ospedale Metropolitano Niguarda	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Istituto Oncologico Veneto Irccs	Padova
Italy	Azienda ULSS 8 Berica	Vicenza
Japan	Aichi Cancer Center Hospital	Aichi
Japan	National Cancer Center Hospital East	Chiba
Japan	National Hospital Organization Shikoku Cancer Center	Ehime
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Hokkaido University Hospital	Hokkaido
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kindai University Hospital	Osaka
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	National Cancer Center Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Korea, Republic of	National Cancer Center (NCC)	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Spain	Hospital Clinico y Provincial de Barcelona	Barcelona
Spain	Hospital Universitari Vall dHebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital-LinKou	Taoyuan
United Kingdom	The Christie	Manchester
United States	Duke University Medical Center	Durham	North Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Norton Cancer Institute Audubon	Louisville	Kentucky
United States	Sarah Cannon (Tennessee Oncology - Nashville)	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Italy,  Japan,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review Following IV Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2-overexpressing Metastatic Colorectal Cancer	Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.	6 months post-dose administration to data cut off, up to 20 months
Secondary	Confirmed Objective Response Rate by Investigator Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer		6 months post-dose administration to data cut off, up to 40 months
Secondary	Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer		6 months post-dose administration to data cut off, up to 40 months
Secondary	Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer		6 months post-dose administration to data cut off, up to 40 months
Secondary	Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer		6 months post-dose administration to data cut off, up to 40 months
Secondary	Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer		6 months post-dose administration to data cut off, up to 40 months
Secondary	Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer		6 months post-dose administration to data cut off, up to 40 months
Secondary	Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer		Baseline up to 40 months
Secondary	Change From Baseline in Patient-Reported Outcomes (PROs) in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30)		Baseline up to 40 months
Secondary	Change From Baseline in Patient-Reported Outcomes (PROs) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Colorectal Cancer 29 (QLQ-CR29)		Baseline up to 40 months
Secondary	Patient-Reported Outcomes (PROs) in the EuroQol Questionnaire (EQ) of 5 Dimensions (5D) on a Standardized 5- Level (5L) Descriptive Health Status Scale (EQ-5D-5L)		Baseline up to 40 months
Secondary	Patient-Reported Outcomes (PROs) in Patient's Global Impression of Treatment Tolerability (PGI-TT)		Baseline up to 40 months
Secondary	Patient-Reported Outcomes (PROs) in Patient Global Impression of Symptom Severity (PGIS)		Baseline up to 40 months
Secondary	Patient-Reported Outcomes (PROs) in Patient Global Impression of Change (PGIC) Scores		Baseline up to 40 months
Secondary	Inpatient Healthcare Resource Utilization		Baseline up to 40 months
Secondary	Serum Concentration of T-DXd		Baseline up to 40 months
Secondary	Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody		Baseline up to 40 months
Secondary	Serum Concentration of Active Metabolite MAAA-1181a		Baseline up to 40 months
Secondary	Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd		Baseline up to 40 months