Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer

Phase 3

Terminated

Interventions: Biological: Futuximab/modotuximab
Drug: Trifluridine/Tipiracil

Brief Summary: This is a randomized phase III study with a safety lead-in part in patients with KRAS/ NRAS and BRAF Wild Type metastatic colorectal cancer who have previously received treatment with oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF agents and anti-EGFR antibodies. The main objective of the safety lead-in part is to assess safety and tolerability of futuximab/modotuximab in combination with trifluridine/tipiracil. The primary objective of the phase III part is to compare Overall Survival of futuximab/modotuximab in combination with trifluridine/tipiracil vs trifluridine/tipiracil monotherapy in patients with tumours that are KRAS/NRAS and BRAF wild-type (WT).

Recruitment & Eligibility

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 ≥ 4 months
Estimated life expectancy ≥ 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate haematological, renal and hepatic function

Exclusion Criteria

Pregnancy, possibility of becoming pregnant during the study, breastfeeding woman
Patients currently receiving or having received anticancer therapies within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part).
Major surgery within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 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 (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 (Phase 3 part)
Prior radiotherapy if completed less than 4 weeks before the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part)
Patients with other malignancies

Arm && Interventions

Group	Intervention	Description
Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)	Futuximab/modotuximab	-
Trifluridine/tipiracil (Phase III part)	Trifluridine/Tipiracil	-
Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)	Trifluridine/Tipiracil	-

Primary Outcome Measures

Name	Time	Method
Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part)	End of cycle 1 (Each cycle is up to 28 days)	DLTs observed during a 28-day period. A DLT is defined as the following: A clinically significant AE graded according to the NCI-CTCAE version 5.0, observed during the initial 28- day treatment period following the first IMP administration. Assessed as unrelated to underlying disease, disease progression, intercurrent illness, or concomitant medications. At least possibly related to the IMPs (futuximab/modotuximab or trifluridine/tipiracil or both) by the investigator and meeting criteria as outlined in the protocol.
Overall Survival (OS) (In Double Negative, KRAS/NRAS and BRAF Wild Type Patients) (Phase III Part)	up to 4 years 9 months	Time elapsed from date of randomization until the date of death from any cause

Secondary Outcome Measures

Name	Time	Method
Adverse Events (Phase III Part)	Through study completion, up to 4 years 9 months	Incidence, severity, and relationship of treatment emergent adverse event and treatment emergent serious adverse event
Progression Free Survival (Phase III Part)	up to 4 years 9 months	Time elapsed from the date of randomization into the study to disease progression/death
Overall Survival (Safety Lead-In Part)	up to 24 months	Time elapsed from the first IMP intake to death
Overall Survival (In Triple Negative) (Phase III Part)	up to 4 years 9 months	Time elapsed from the date of randomization into the study to disease progression/death

Locations (15): National Cancer Center Hospital East
🇯🇵
Chiba, Japan
University of Michigan Oncology Clinic | Rogel Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
UZA Edegem
🇧🇪
Edegem, Belgium
CHUUCL Namur site Godinne
🇧🇪
Yvoir, Belgium
Docrates cancer center
🇫🇮
Helsinki, Finland
TAYS (Tampere University Hospital)
🇫🇮
Tampere, Finland
Debreceni Egyetem, Klinikai Központ Onkológiai Klinika
🇭🇺
Debrecen, Hungary
Magyar Honvédség Egészségügyi Központ Onkológiai Osztály
🇭🇺
Budapest, Hungary
Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudomáyi Kar Oktatókórháza
🇭🇺
Kecskemét, Hungary
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Onkoterápiás Klinika
🇭🇺
Szeged, Hungary
Odense Universitetshospital
🇩🇰
Odense, Denmark
Rigshospitalet
🇩🇰
Copenhagen, Denmark
Herning Regional Hospital (Regionhospitalet Godstrup)
🇩🇰
Herning, Denmark
Cleveland Clinic Cleveland Clinic Lerner College of Medicine
🇺🇸
Cleveland, Ohio, United States
UZ Leuven Campus Gasthuisberg
🇧🇪
Leuven, Belgium