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) and, unless contraindicated, an anti- vascular endothelial growth factor (VEGF) agent.MedDRA version: 21.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004418-32-IT
- Lead Sponsor
- DAIICHI SANKYO INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 80
Subjects must satisfy all of the following criteria to be included in the
study:
1. Sign and date the ICF prior to the start of any study-specific qualification procedures.
2. Male or female subjects =18 years (follow local regulatory requirements if the legal age of consent for study participation is >18
years old).
3. Pathological or histological confirmation and documentation of colon or rectum adenocarcinoma with advanced or metastatic disease.
4. Must be resistant, refractory, or intolerant to at least 2 prior lines of 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)
5. Has at least 1 measurable lesion confirmed by BICR as per RECIST v1.1.
6. Willing to provide required archival and pre-treatment tumor biopsy for 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. Archival tissue must be available and of sufficient quantity, as defined above, at the time of screening. If archival tissue 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-study tumor biopsy. When at least 10 on-study 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, 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
1. History of ILD (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screen.
2. Clinically severe pulmonary compromise (based on PI's assessment) resulting from intercurrent pulmonary illnesses includ., 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 pneumonectomy.
3. Is receiv. chronic systemic corticosteroids dosed at >10 mg prednisone or equiv. or any form of immunosuppr. therapy prior to Cycle 1 Day 1. Subj. who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study.
4. Evidence of leptomeningeal disease
5. Has clinically active spinal cord compression or brain metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subj. with clinically inactive brain metastases may be included in the study. Subj. with treated brain metastases who 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 effects of radiotherapy.
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. Immune checkpoint inhibitor therapy <21 days;
d. Major surgery (excl. placement of vascular access) <4 weeks;
e. Radiotherapy treatment to >30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 d;
f. Chloroquine or hydroxychloroquine =14 days.
7. Prior treat. with an anti-HER3 antibody and/or 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. Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor (Medical Monitor or designee).
9. Had primary malignancies other than CRC within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ dis., or other solid tumors curatively treated.
10. Uncontrolled or sign. cardiovascular dis. prior to Cycle 1 Day 1, including:
a. QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation interval of >470 milliseconds (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. Uncont. hypertension (resting systolic blood press. >180 mmHg or diastolic blood press. >110 mmHg) within 28 days;
d. Myocardial infarction within 6 months;
e. NYHA Classes 2 to 4 within 28 days;
f. Uncontrolled angina pectoris within 6 mths
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