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). MedDR
Conditions
Interventions
Product Code: U3-1402
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Patritumab deruxtecan
CAS Number: N/A
Current Sponsor code: U3-1402
Other descriptive name: N/A
Concent
Sponsors
DAIICHI SANKYO, INC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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 30% of the bone marrow or with a wide field of radiation 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the tolerability and antitumor activity of U3-1402 in subjects with advanced or metastatic CRC who are resistant, refractory, or intolerant to at least 2 prior lines of therapy ;Secondary Objective: To investigate the durability of U3-1402 antitumor activity in subjects with advanced or metastatic CRC To further investigate the antitumor activity of U3-1402 in subjects with advanced or metastatic CRC To evaluate the safety and tolerability of U3 1402 in subjects with advanced or metastatic CRC To evaluate HER3 protein expression in tumor tissue and its relationship with efficacy To assess the immunogenicity incidence against U3-1402 To characterize the 3 PK analytes of U3-1402 in subjects with advanced or metastatic CRC;Primary end point(s): Objective Response Rate (ORR) is defined as the proportion of subjects with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR). ;Timepoint(s) of evaluation of this end point: Data are collected at baseline, then from the start of study treatment until disease progression or by BICR, death, lost to follow-up, or withdrawal of consent by the subject. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Duration of Response (DoR) is defined as the time from the first documented response (complete response [CR] or partial response [PR]) to the date of disease progression or death due to any cause. Objective Response Rate (ORR) is defined as the proportion of subjects with a best overall response (BOR) of confirmed CR or PR. Duration of Response (DoR) is defined as the duration from the first documented response to the date of disease progression or death due to any cause. Disease Control Rate (DCR) is defined as the proportion of subjects who achieved a confirmed BOR of CR, PR, or stable disease (SD). Time to Tumor Response (TTR) is defined as the time from the start of study treatment to the date of the first documentation of objective response (CR or PR) that is subsequently confirmed. Progression-Free Survival (PFS) is defined as the duration from the start of study treatment to the date of the first documentation of objective progressive disease (PD) or death due to any cause, whichever is earlier. Overall Survival (OS) is defined as the time from the start of study treatment to the date of death due to any cause. Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse event of special interests (AESIs) (ILD and elevation of aminotransferases and TBL), ECOG PS, vital sign measurements, standard clinical laboratory parameters. AEs will be coded using the most recent version of MedDRA and will be graded using NCI-CTCAE v5.0. HER3 protein expression in tumor tissue (as determined by IHC) and correlation with efficacy Anti-drug Antibody (ADA) prevalence: The proportion of all subjects having a confirmed positive ADA sample at any point in time. ADA incidence: The proportion of subjects having treatment-emergent ADA. ADA titer will be determined for confirmed ADA-positive samples. Neutralizing antibodies: When neutralizing assay becomes available, confirmed ADA-positive samples may be analyzed for | — |
Countries
Belgium, France, Italy, Japan, Poland, Spain, United Kingdom, United States
Contacts
Public ContactLisa Ochsner
Syneos Health LLC
Outcome results
None listed