Metastatic colorectal cancer MedDRA version: 21.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Institut de Recherches Internationales Servier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically or cytologically confirmed adenocarcinoma of metastatic colorectal cancer (mCRC), not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumour Without RAS (KRAS and NRAS) and BRAF V600E mutations based on Circulating tumour DNA (ctDNA) screening blood test analysis - Participants with measurable or non-measurable lesion - Participants must have received at least 2 prior regimens of standard chemotherapy for mCRC and had demonstrated progressive disease or intolerance to their last regimen - Participants should have received previous treatment with commercially available anti-EGFR mAbs for = 16 weeks. - Estimated life expectancy = 12 weeks - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Adequate haematological function - Adequate renal function - Adequate hepatic function - Serum potassium, serum phosphates, serum magnesium within normal limits 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 275 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 225
Exclusion criteria
Exclusion criteria: - Pregnancy, possibility of becoming pregnant during the study, breast-feeding woman - Patients currently receiving or having received anticancer therapies within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Randomised part) - Major surgery within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Randomised part) or participants who have not recovered from side effects of the surgery - Participants with serious/active/uncontrolled infection - Known clinically significant cardiovascular disease or condition - Significant gastrointestinal abnormality - Skin rash of Grade > 1 from prior anti-EGFR at the time of inclusion (Safety Lead-in part) or randomization (Randomised Phase 3 part), or any other skin toxicity precluding participation in the study according to investigator's discretion - Treatment with systemic immunosuppressive therapy within 4 weeks prior to inclusion (Safety Lead-in part) or randomization (Randomised part) - Prior radiotherapy if completed less than 4 weeks before the inclusion visit (Safety Lead-in part) or randomization visit (Randomised part) - Patients with other malignancies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety Lead-In part: - Assess safety and tolerability of futuximab/modotuximab (S95026) in combination with trifluridine/tipiracil. Randomised part: - Compare overall survival (OS) of futuximab/modotuximab in combination with trifluridine/tipiracil versus trifluridine/tipiracil monotherapy in participants with tumours that are KRAS/NRAS and BRAF wild-type (WT) (Double negative).;Secondary Objective: Safety Lead-In pat: - Assess anti-tumor activity of S95026 combined with trifluridine/tipiracil - Characterize the pharmacokinetic (PK) profile of S95026, trifluridine and tipiracil in the combination of S95026 with trifluridine/tipiracil - Evaluate the immunogenicity of S95026 Randomised part: - Compare OS of S95026 combined with trifluridine/tipiracil vs trifluridine/tipiracil monotherapy in participants with tumours that are KRAS/NRAS, BRAF, and EGFR-extracellular domain WT - Compare anti-tumour activity of S95026 combined with trifluridine/tipiracil vs trifluridine/tipiracil monotherapy - Evaluate, compare the safety of S95026 combined with trifluridine/tipiracil vs trifluridine/tipiracil monotherapy - Compare Quality of life of S95026 combined with trifluridine/tipiracil vs trifluridine/tipiracil monotherapy - Characterize the PK profile of S95026, trifluridine and tipiracil when S95026 combined with trifluridine/tipiracil - Evaluate the immunogenicity of S95026;Primary end point(s): Safety Lead-In part: - Incidence of dose-limiting toxicities (DLTs) Randomised part: - OS (In double negative);Timepoint(s) of evaluation of this end point: Safety Lead-In part: - During the initial 28 day treatment period (Cycle 1) Randomised part: - From the date of randomisation into the study to death from any cause | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Lead-In part: - Objective Response (OS) - Best Overall Response (BOR) - Disease Control Rate (DCR) - Progression Free Survival (PFS) - OS - Derived PK parameters for futuximab/modotuximab, trifluridine and tipiracil - Anti-drug antibody (ADA) development Randomised part: - Key endpoint: OS (participants with tumours that are KRAS/NRAS, BRAF, and EGFR-extracellular domain WT) - PFS - OR - DCR - Duration of response (DoR) - Time to Response (TTR) - Time to Next Treatment (TTNT) - Time to ECOG Performance Status =2 (TtPS2) - TEAEs, STEAEs, AEs - Vital signs, key laboratory assessment - European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EQ-5D-5L questionnaires - Dervied PK parameter - ADA development;Timepoint(s) of evaluation of this end point: Safety Lead-in part: - OR, DCR: all along the study - BOR: Screening, through disease progression/recurrence - PFS: From the first IMP intake to disease progression/death - OS: From the first IMP intake to death - EPK parameters, ADA: very week each cycle Randomised part: - OS, PFS: Randomization to disease progression/death - OR, DCR, AEs, TEAEs, STEAEs: all along the study - DoR: first tumour response to disease progression/death - TTR: randomization to first tumour response - TTNT: randomization to initiation of the next therapy - TtPS2: randomization to ECOG PS score of =2 - Vital signs: baseline to last-post-baseline value under treatment - QoL: baseline, C2D1, from C3D1 every 2 cycles in treatment period, withdrawal visit, every 8 weeks in FU until study end/death | — |
Countries
Belgium, Brazil, Denmark, Finland, Hungary, Japan, Poland, United States
Contacts
Public ContactClinical Studies Department
Institut de Recherches Internationales Servier
Outcome results
None listed