Study of U3-1402 in subjects with colorectal cancer
- Conditions
- Advanced or metastatic colorectal cancer (CRC) which is resistant, refractory, or intolerant to at least 2 prior lines of therapy, that must include all of the following agents: fluoropyrimidine, irinotecan, platinum agent, an anti-epidermal growth factor receptor (EGFR) agent (if clinically indicated), an anti-vascular endothelial growth factor (VEGF) agent (if clinically indicated), an immune checkpoint inhibitor (if clinically indicated), and a BRAF inhibitor (if clinically indicated).MedDRA version: 21.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004418-32-GB
- Lead Sponsor
- DAIICHI SANKYO, INC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 80
Subjects must satisfy all of the following criteria to be included in the study:
1. Subject has provided written informed consent prior to the start of
any study-specific procedures.
2. Subjects =18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
3. Pathological/histological confirmation of advanced or metastatic colon or rectal adenocarcinoma.
4. Must be resistant, refractory, or intolerant to at least 2 prior lines of systemic therapy, that must include all of the following agents:
a. Fluoropyrimidine
b. Irinotecan
c. Platinum agents (eg, oxaliplatin)
d. An anti-EGFR agent, if clinically indicated (eg, RAS/BRAF wildtype)
e. An anti-VEGF agent, unless contraindicated (eg, bevacizumab)
f. An immune checkpoint inhibitor, if clinically indicated (eg,
microsatellite instability-high [MSI-H] status)
g. A BRAF inhibitor, if clinically indicated (eg, BRAF V600E positive)
5. Has at least 1 measurable lesion confirmed by blinded independent central review (BICR) as per (RECIST) Version (v) 1.1.
6. Willing to provide a required pre-treatment tumor biopsy and an
additional archival tissue sample for the assessment of HER3 expression levels by IHC and exploratory biomarkers, defined as:
a. Pre-treatment tumor biopsy. Subjects may be exempted from the requirement to provide a pre-treatment tumor biopsy if archival tumor tissue was collected within 3 months of screening during or after treatment with the last prior cancer treatment and is of sufficient quantity (2 cores or 20 slides with adequate tumor tissue content).
b. An additional archival tissue sample collected greater than 3 months prior to screening must be available and of sufficient quantity, as defined above, at the time of screening. If an archival tissue sample (collected greater than 3 months prior to screening) is not available, a subject may be included provided the pre-treatment tumor biopsy is obtained and after discussion and agreement from Sponsor (Medical Monitor or designee).
c. Consent to provide on-treatment tumor biopsy. When at least 10 on-treatment tumor biopsies per cohort have been collected, the Sponsor will provide written notification of a change to the requirement.
7. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
8. Life expectancy =3 months.
9. Has adequate bone marrow reserve and organ function at baseline based on local laboratory data, defined as within 14 days prior to Cycle 1 Day 1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8
Subjects who meet any of the following criteria will be denied entry to the study:
1. Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.
2. Clinically severe pulmonary compromise (based on Investigator’s assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
a. any underlying pulmonary disorder (eg, pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion)
b. any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis)
OR prior complete pneumonectomy.
3. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
4. Evidence of leptomeningeal disease
5. Evidence of clinically active spinal cord compression or brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are
asymptomatic (ie, without neurologic signs or symptoms and do not
require treatment with corticosteroids or anticonvulsants) may be
included in the study. Subjects must have a stable neurologic status for
at least 2 weeks prior to Cycle 1 Day 1.
6. Inadequate washout period prior to Cycle 1 Day 1 of U3-1402:
a. Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days;
b. Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study <14 days or 5 half-lives, whichever is longer;
c. Monoclonal antibodies other than immune checkpoint inhibitors, such
as bevacizumab (anti-VEGF) and cetuximab (anti-EGFRs) <28 days;
d. Immune checkpoint inhibitor therapy <21 days;
e. Major surgery (excluding placement of vascular access) <4 weeks;
f. Radiotherapy treatment to >30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days;
g. Chloroquine or hydroxychloroquine <14 days.
7. Prior treatment with an anti-HER3 antibody and/or antibody drug conjugate (ADC) that consists of an exatecan derivative that is any topoisomerase I inhibitor (eg, trastuzumab deruxtecan).
8. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 Grade =1 or baseline.
9. Had primary malignancies other than CRC within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.
10. Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1, including:
a. QT interval corrected for heart rate using Fridericia’s formula prolongation interval of >470 (ms) for females and >450 ms for males within 28 days;
b. Left ventricular ejection fraction (LVEF) <50% by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within 28 days;
c. Resting systolic blood pres
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method