Trastuzumab deruxtecan for subjects with HER2-overexpressing advanced or metastatic CRC (DESTINY-CRC02)

JRCT ID: jRCT2051200124

Registered date:29/01/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Subjects with HER2-overexpressing locally advanced, unresectable, or metastatic colorectal cancer.
• Date of first enrollment: 17/03/2021
• Target sample size: 120
• Countries of recruitment: Australia,Japan,Belgium,Japan,France,Japan,Italy,Japan,SK,Japan,Spain,Japan,Taiwan,Japan,UK,Japan,USA,Japan
• Study type: Interventional

Intervention(s)

- T-DXd 5.4 mg/kg Q3W
Participants will be randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg Q3W.

- T-DXd 6.4 mg/kg Q3W
Participants will be randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg Q3W.

Outcome(s)

• Primary Outcome: To assess the efficacy of trastuzumab deruxtecan (T-DXd), as measured by the confirmed ORR by BICR in HER2-overexpressing (defined as IHC 3+ or IHC2+/ISH+) mCRC subjects treated at the 5.4 mg/kg and 6.4 mg/kg doses

Secondary Outcome

- To evaluate the clinical efficacy of T-DXd by confirmed ORR by Investigator assessment
- To evaluate the clinical efficacy of T-DXd by DoR
- To further evaluate the clinical efficacy of T-DXd by DCR, CBR, PFS, and OS
- To further evaluate the safety and tolerability of T-DXd
- To evaluate HEOR endpoints including patient-reported HRQoL, symptoms, and physical functioning
- To evaluate healthcare resource utilization for both treatment arms
- To evaluate PK of T-DXd
- To evaluate immunogenicity of T-DXd

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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 BRAF wild-type
cancer and RAS status identified in primary or metastatic site.
3. The following therapies should be included in prior lines of therapy:
a. Fluoropyrimidine, oxaliplatin, and irinotecan, unlesscontraindicated
b. Anti-EGFR treatment, if RAS wild-type and if clinically indicated
c. Anti-VEGF treatment, if clinically indicated
d. Anti-PD-(L)-1 therapy, if tumor is MSI-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high, if clinically indicated
4. Confirmed HER2-overexpressing status assessed by central laboratory
and defined as IHC 3+ or IHC 2+/ISH+.
5. Presence of at least one measurable lesion assessed by the Investigator
per RECIST version 1.1.
6. ECOG PS of 0 or 1.
7. Has LVEF >=50% within 28 days before randomization/registration.

Exclude criteria

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 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 (QTcF) prolongation to >470 msec (female participants) or >450 msec (male participants) based on the average of the Screening triplicate 12-lead ECGs.
3. Has a history of (non-infectious) 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, Sjogren 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 RNA.
11. Previous treatment with a DXd-containing ADC.

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT04744831