Trastuzumab deruxtecan for subjects with HER2-overexpressing advanced or metastatic CRC

Phase 1

• Conditions: HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal Cancer; MedDRA version: 21.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004782-39-FR
• Lead Sponsor: Daiichi Sankyo Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-01
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 122

Inclusion Criteria

1. Sign and date the Tissue Pre-Screening and Main ICFs, prior to the start of any respective study-specific qualification procedures.
2. Adults aged =20 years in Japan, Taiwan, and Korea, or those aged = 18 years in other countries, at the time the ICFs are signed. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 years).
3. Pathologically-documented, unresectable, recurrent, or metastatic colorectal adenocarcinoma. Subject must have BRAF wild-type cancer and RAS status identified in primary or metastatic site, tested by a Clinical Laboratory Improvement Act (CLIA), ISO15189, or equivalent-certified laboratory.
4. The following therapies should be included in prior lines of therapy:
a. Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated
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
5. Is willing and able to provide an adequate tumor sample for tissue pre-screening to confirm HER2 status by central laboratory (most recent tumor tissue preferred).
6. Confirmed HER2-overexpressing status assessed by central laboratory and defined as IHC 3+ or IHC 2+/ISH+.
7. Presence of at least one measurable lesion assessed by the Investigator per RECIST version 1.1. Lesions situated in a previously-irradiated area are considered measurable if progression has been demonstrated in such lesions after the end of radiotherapy.
8. ECOG PS of 0 or 1.
9. Has LVEF =50% within 28 days before randomization/registration.
10. Has adequate organ function within 14 days before randomization/registration as defined in the protocol.
11. Has adequate treatment washout period before randomization/registration as defined in the protocol.
12. If the subject is a woman of childbearing potential, she must have a negative urine pregnancy test within 72 hours before randomization/registration; a positive urine pregnancy test result must immediately be confirmed using a serum test. The subject must also be willing to use highly effective birth control, as detailed in Section 10.3.4, upon randomization/registration, during the Treatment Period, and for 7 months, following the last dose of study drug. A woman is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral
salpingectomy, or bilateral oophorectomy).
a. Non-childbearing potential is defined as premenopausal female subjects with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone [FSH] >40 mIU/mL and estradiol <40 pg/mL [<147 pmol/L] is confirmatory). Female subjects on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of childbearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to randomization/registration. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type

Exclusion 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). Subjects 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 subjects) or >450 msec (male subjects) 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, Sjögren syndrome, sarcoidosis, etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of Screening. Full details of the disorder should be recorded in the electronic case report form (eCRF) for subjects who are included in the study.
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. Subjects with clinically inactive brain metastases may be included in the study. Subjects 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. Subjects with leptomeningeal carcinomatosis.
9. Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated.
10. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
11. Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
12. Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
13. Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions that may in the opinion of the Investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results.
14. Has known human immunodeficiency virus (HIV) infection. Unless required by local regulations or institutional review board (IRB)/ethics committee (EC), an HIV antigen/antibody test is not required prior to randomization/enrollment.
15. Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days before study randomization/registration. Subjects 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified