Metastatic Colorectal Cancer and Acquired Resistance to Anti-EGFR Monoclonal Antibodies and Documented Mutation of Extra Cellular Doman of EGFR MedDRA version: 19.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Sym004
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Futuximab
CAS Number: 1310460-85-5
Current Sponsor code: 992DS
Other descriptive name: SYM004
Concentration unit: m
Sponsors
Symphogen A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written informed consent obtained before undergoing any study-related activities • Male or female, at least 18 years of age • Histologically or cytologically confirmed locally advanced or metastatic CRC that is documented to be without KRAS or NRAS gene mutations (i.e. tumors must express the KRAS and NRAS wild type (WT) exon 2, 3, and 4) • Identification of any ECD-EGFR mutation in blood sample • Failure of or intolerance to all of the following a. Fluorouracil (5-FU) b. Oxaliplatin c. Irinotecan • Previous treatment with bevacizumab and/or ziv-aflibercept is allowed, but not mandatory. • “Acquired resistance” to marketed anti-EGFR mAbs a. Response while on previous treatment with marketed anti-EGFR mAb, defined as i. Partial response (PR) or complete response (CR) and/or ii. Stable disease (SD) for more than 16 weeks b. Documented progressive disease (PD) during or within 3 calendar months after cessation of previous anti-EGFR mAb treatment • No more than 3 calendar months from last dose of previous anti-EGFR mAb to time of consent • Measurable disease defined as one or more target lesions according to RECIST 1.1 • Life expectancy of at least 3 months • ECOG PS = 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: • Intake of any investigational drug or any anticancer therapy in the 28 days (or 5 half-lives for noncytotoxics, whichever is shorter) before the first dose of IMP • Previous treatment with Sym004, TAS-102 (trifluridine and tipiracil [Lonsurf®]) and/or regorafenib [Stivarga®] • Patients who in the opinion of the Investigator would benefit more from regorafenib or Lonsurf® treatment (except where regorafenib or Lonsurf® are not reimbursed in the country) • Diarrhea Common Terminology Criteria for Adverse Events (CTCAE) Grade >1 at Screening (Step 1) • Skin rash CTCAE Grade >1 from previous anti-EGFR therapy at Screening (Step 1) • Magnesium <0.9 mg/dL • Abnormal organ or bone marrow function
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of the weekly dosing regimen (9 mg/kg loading dose followed by 6 mg/kg/week dose) of Sym004 in terms of overall response rate (ORR) in patients with mCRC harboring ECD-EGFR mutations;Secondary Objective: • To assess efficacy in terms of duration of response (DOR), progression-free survival (PFS), time-to-treatment failure (TTF), and overall survival (OS) • To determine the safety profile of the weekly dosing regimen • To evaluate the dose intensity for the weekly dosing regimen • To evaluate pharmacokinetics and immunogenicity of Sym004;Primary end point(s): Documented best overall response (OR), assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on Investigator assessment.;Timepoint(s) of evaluation of this end point: Response (CR, PR, PD, or SD) will initially be evaluated per RECIST v1.1 by the Investigator. All scans from responders from Stage 1 of the trial will be subject for central evaluation at the timepoint of the futility assessment and all the rest will be evaluated at the end of the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • DOR, which is defined as time from first documentation of tumor response (complete response [CR] or partial response [PR]) to disease progression • PFS, which is defined as the duration from the first dose of Sym004 until first event, where an event can be a progression (radiological confirmation or clinical progression) or death due to any cause, where death will only be considered as an event if it occurs within 12 weeks after last tumor response assessment without progression • TTF, which is defined as time from the first dose until discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death • OS, which is defined as the time from the first dose to the date of death. If a patient has not died, his survival time will be censored at the last date he was known to be alive • Pharmacokinetic (PK) parameters for Sym004 describing systemic exposure, half-life, clearance, and volume of distribution;Timepoint(s) of evaluation of this end point: DOR is defined as time from first documentation of tumor response to disease progression PFS is defined as the duration from the first dose of Sym004 until first event, where an event can be a progression or death due to any cause, where death will only be considered as an event if it occurs within 12 weeks after last tumor response assessment without progression TTF is defined as time from the first dose until discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death OS is defined as the time from the first dose to the date of death. If a patient has not died, his survival time will be censored at the last date he was known to be alive PK - throughout study until end of treatment visit | — |
Countries
Italy, Spain
Contacts
Public ContactIvan Horak
Symphogen A/S
Outcome results
None listed