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

A Randomised, Open-label, Multi-centre, Two-arm Phase 3 Study Comparing Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil to Trifluridine/Tipiracil Single Agent With a Safety Lead-In Part in Participants With KRAS/NRAS and BRAF Wild Type Metastatic Colorectal Cancer Previously Treated With Standard Treatment and Anti-EGFR Therapy

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).

Study Overview

• Status: Terminated
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Biological: Futuximab/modotuximab; Drug: Trifluridine/Tipiracil; Drug: Trifluridine/Tipiracil

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Institut de Recherches Internationales Servier, Clinical Studies Department; Phone Number: +33 1 55 72 43 66; Email: scientificinformation@servier.com

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • UZA Edegem
  • Leuven, Belgium, 3000
    • UZ Leuven campus Gasthuisberg
  • Yvoir, Belgium, 5530
    • CHUUCL Namur site Godinne
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Herning, Denmark, 7400
    • Herning Regional Hospital (Regionhospitalet Godstrup)
  • Odense, Denmark, 5000
    • Odense Universitetshospital
• Finland
  • Helsinki, Finland, 00180
    • Docrates Cancer Center
  • Tampere, Finland, 33520
    • TAYS (Tampere University Hospital)
• Hungary
  • Budapest, Hungary, 1062
    • Magyar Honvédség Egészségügyi Központ Onkológiai Osztály
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem, Klinikai Központ Onkológiai Klinika
  • Kecskemét, Hungary, 6000
    • Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudomáyi Kar Oktatókórháza
  • Szeged, Hungary, 6720
    • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ Onkoterápiás Klinika
• Japan
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East
• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Oncology Clinic | Rogel Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Cleveland Clinic Lerner College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)	Biological: Futuximab/modotuximab; Concentrate for solution for infusion, futuximab/modotuximab will be administered via IV route, once weekly of each cycle at 9 mg/kg/dose at Cycle 1 Day 1 and then at 6 mg/kg/dose. Each cycle is up to 28 days.; Drug: Trifluridine/Tipiracil; Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) will be administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle will be repeated every 28 days.; Drug: Trifluridine/Tipiracil; Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) will be administered orally twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle will be repeated every 28 days.
Active Comparator: Trifluridine/tipiracil (Phase III part)	Drug: Trifluridine/Tipiracil; Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) will be administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle will be repeated every 28 days.; Drug: Trifluridine/Tipiracil; Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) will be administered orally twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle will be repeated every 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-limiting Toxicities (DLTs) (Safety Lead-In Part)	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.	End of cycle 1 (Each cycle is up to 28 days)
Overall Survival (OS) (In Double Negative, KRAS/NRAS and BRAF Wild Type Patients) (Phase III Part)	Time elapsed from date of randomization until the date of death from any cause	up to 4 years 9 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company
• Investigators: Principal Investigator: Fortunato Ciardiello, University of Campania "Luigi Vanvitelli"

Publications and helpful links

Helpful Links

• Find Results on Servier Clinical Trial Data website

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2022
• Primary Completion (Actual): June 21, 2023
• Study Completion (Actual): June 21, 2023

Study Registration Dates

• First Submitted: January 25, 2022
• First Submitted That Met QC Criteria: January 25, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Phase III; EGFR; Adult; Metastatic; Colorectal Cancer; Trifluridine/tipiracil; Colorectal; Sym004; Futuximab/modotuximab; Safety Lead-In part; S95026
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Trifluridine
• Other Study ID Numbers: CL3-95026-001; 2021-003151-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).

where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

sponsored by Servier with a first patient enrolled as of 1 January 2004 onwards for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
2. Study Protocol
3. Statistical Analysis Plan
4. Informed Consent Form
5. Clinical Study Report
6. Study-level clinical trial data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No