Study of Tepotinib Combined With Cetuximab in Participants With Left-Sided RAS/BRAF Wild Type Metastatic Colorectal Cancer (PERSPECTIVE)

NCT ID: NCT04515394

Last Updated: 2022-12-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-28
• Study Completion Date: 2022-03-31

Brief Summary

The purpose of this study was to assess the preliminary antitumor activity, safety and tolerability of tepotinib in combination with cetuximab in participants with RAS/BRAF wild-type left-sided Metastatic Colorectal Cancer (mCRC) having acquired resistance to anti-epidermal growth factor receptor (EGFR) antibody targeted therapy due to mesenchymal epithelial transition (MET) amplification.

Conditions

Colorectal Neoplasms

Keywords

Colorectal cancer; RAS wild-type; Tepotinib; Cetuximab; Erbitux; Epidermal growth factor receptor resistance; Hepatocyte growth factor; Panitumumab; Mesenchymal epithelial transition

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tepotinib + Cetuximab

Group Type: EXPERIMENTAL

Tepotinib

Intervention Type: DRUG

Participants received Tepotinib film-coated tablets at a dose of 500 milligrams (mg) orally, once daily (QD) until disease progression (according to Response Evaluation Criteria in Solid Tumors Version 1.1 \[RECIST v1.1\]), death, Adverse event (AE) leading to discontinuation, study withdrawal, or withdrawal of consent, whichever occurs first.

Cetuximab

Intervention Type: BIOLOGICAL

Participants received weekly intravenous infusions of Cetuximab at a dose of 250 milligrams per square meter (mg/m\^2) until disease progression (according to Response Evaluation Criteria in Solid Tumors Version 1.1 \[RECIST v1.1\]), death, Adverse event (AE) leading to discontinuation, study withdrawal, or withdrawal of consent, whichever occurs first.

Interventions

Tepotinib

Participants received Tepotinib film-coated tablets at a dose of 500 milligrams (mg) orally, once daily (QD) until disease progression (according to Response Evaluation Criteria in Solid Tumors Version 1.1 \[RECIST v1.1\]), death, Adverse event (AE) leading to discontinuation, study withdrawal, or withdrawal of consent, whichever occurs first.

Intervention Type: DRUG

Cetuximab

Participants received weekly intravenous infusions of Cetuximab at a dose of 250 milligrams per square meter (mg/m\^2) until disease progression (according to Response Evaluation Criteria in Solid Tumors Version 1.1 \[RECIST v1.1\]), death, Adverse event (AE) leading to discontinuation, study withdrawal, or withdrawal of consent, whichever occurs first.

Intervention Type: BIOLOGICAL

Other Intervention Names

MSC2156119J; Erbitux®; MSB0010442D

Eligibility Criteria

Inclusion Criteria

• Advanced (locally advanced or metastatic) left sided (from splenic flexure to rectum - National Comprehensive Cancer Network [NCCN] version 4.2020) colorectal cancer (CRC) with RAS/BRAF wild-type at study entry confirmed prior to enrollment, with previous anti-epidermal growth factor receptor (anti-EGFR) therapy and acquired resistance on the most recent anti-EGFR monoclonal antibody therapy (panitumumab or cetuximab) by radiological documentation of disease progression according to RECIST Version 1.1
• Mesenchymal epithelial transition (MET) amplification detected by a positive liquid biopsy and/or tissue with appropriate regulatory status (collected after disease progression of the previous anti-EGFR therapy)
• Measurable disease by Investigator in accordance with RECIST Version 1.1
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
• Life expectancy greater than 3 months
• Participants having at least one systemic treatment for mCRC including 1 anti-EGFR monoclonal antibody therapy as the most recent line of therapy for mCRC before study treatment and must have shown a radiologically confirmed by RECIST Version 1.1 complete response (CR) or partial response (PR), both for at least 4 months or stable disease (SD) for at least 6 months to that therapy prior to disease progression
• Less than 2 months between the last administration of the most recent EGFR containing regimen and first dosing in this study
• Adequate hematological function, hepatic and renal functions as defined in the protocol
• Signed and dated informed consent indicating that the participants had been informed of all the pertinent aspects of the trial prior to enrollment
• Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies

Exclusion Criteria

• Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS metastases. Also excluded are participants with carcinomatous meningitis
• Participants who have brain metastasis as the only measurable lesion
• Prior chemotherapy, biological therapy, radiation therapy, hormonal therapy for anti-cancer purposes, targeted therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of study intervention, except for the anti-EGFR containing regimen including associated chemotherapy if applicable, which may be continued until enrollment of the participant in the study
• Any unresolved toxicity Grade 2 or more according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, from previous anticancer therapy excluding neuropathy, alopecia and rash
• Severe hypersensitivity reactions to monoclonal antibodies (Grade greater than or equal to [>=] 3 NCI-CTCAE v 5.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more occurrences of partially controlled asthma)
• Discontinuation of the most recent cetuximab or panitumumab containing therapy due to an adverse event
• Prior treatment with other agents targeting the hepatocyte growth factor (HGF)/Mesenchymal epithelial transition (MET) pathway
• Impaired cardiac function: Left ventricular ejection fraction less than [<] 45 percent [%] defined by echocardiography (a screening assessment not required for participants without a history of congestive heart failure unless clinically indicated); Serious arrhythmia; Unstable angina pectoris; New York Heart Association heart failure Class III and IV; Myocardial infarction within the last 12 months prior to study entry and Symptomatic pericardial effusion; Corrected QT interval by Fridericia (QTcF) greater than (>) 480 milliseconds (ms)
• Hypertension uncontrolled by standard therapies (not stabilized to less than [< ]150/90 millimeter of mercury [mmHg])
• History of neoplasm other than mCRC
• History of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the test products
• Known infection with human immunodeficiency virus, or an active infection with hepatitis B or hepatitis C virus
• Major surgery within 28 days prior to Day 1 of study intervention
• History of Interstitial lung disease (ILD) or interstitial pneumonitis including radiation pneumonitis that required steroid treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

Mayo Clinic

Phoenix, Arizona, United States

Moores Cancer Center

La Jolla, California, United States

University of California, Los Angeles (UCLA)

Santa Monica, California, United States

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, United States

Mayo Clinic Hospital

Jacksonville, Florida, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Mayo Clinic

Rochester, Minnesota, United States

North Shore-LIJ Monter Cancer Center

Lake Success, New York, United States

Allegheny-Singer Research Institute

Pittsburgh, Pennsylvania, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Scott & White Vasicek Cancer Treatment Center

Temple, Texas, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Aurora Cancer Care - Milwaukee West

Wauwatosa, Wisconsin, United States

Antwerp University Hospital

Antwerp, , Belgium

UZ Leuven

Leuven, , Belgium

Universtity Hospital Brno

Brno, , Czechia

University Hospital Olomouc

Olomouc, , Czechia

Dept. of Oncology Faculty Hospital Motol

Prague, , Czechia

Hospital Na Bulovce

Prague, , Czechia

CHU Besançon Hôpital Jean Minjoz

Besançon, , France

University Hospital of Besançon

Besançon, , France

CHU Estaing

Clermont-Ferrand, , France

CHU Hôpital Henri Mondor

Créteil, , France

Clinique Victor Hugo

Le Mans, , France

CHU de Poitiers

Poitiers, , France

Curie Institute

Saint-Cloud, , France

Institut Curie - René-Huguenin Hospital

Saint-Cloud, , France

Istituto Scientifico Romagnolo per lo Studio e la Cura die Tumori

Meldona, , Italy

Fondazione IRCCS - Istituto Tumori Milano

Milan, , Italy

Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Istituto Nazionale Tumori, Fondazione G. Pascale Napoli

Napoli, , Italy

UOC Oncoematologia AOU Vanvitelli

Napoli, , Italy

Istituto Oncologico Veneto IRCCS

Padua, , Italy

Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chiara

Pisa, , Italy

Fondazione Policlinico Universitario Agostino Gemelli

Rome, , Italy

Foundation IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo FG, , Italy

Arkangelsk Clinical Oncological Dyspensary

Arkhangelsk, , Russia

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

Chelyabinsk, , Russia

Kursk Regional Clinical Oncology Dispensary

Kislino, , Russia

FSBI "National Medical Research Center of Oncology n.a. N.N. Blokhina" of the MoH of the RF

Moscow, , Russia

Limited Liability Company Medicine 24/7

Moscow, , Russia

Russian Cancer research center n.a. N.N. Blokhin

Moscow, , Russia

Omsk Regional Oncology Dispensary

Omsk, , Russia

LLC Clinica UZI 4D

Pyatigorsk, , Russia

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, , Russia

Tomsk National Research Medical Center

Tomsk, , Russia

MKMC Medical City

Tyumen, , Russia

SAHI Republican Clinical Oncology Dispensary

Ufa, , Russia

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

VHIO Valle de Hebron Instituto de Oncologia

Barcelona, , Spain

H.U. Ramon y Cajal

Madrid, , Spain

HM-CIOCC

Madrid, , Spain

Hospital de Madrid Norte Sanchinarro

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital UNiversitario La Paz

Madrid, , Spain

H.U.Marqués de Valdecilla

Santander, , Spain

HUVirgen del Rocio

Seville, , Spain

Consorcio Hospital General Universitario de Valencia

Valencia, , Spain

Bristol Oncology Centre

Bristol, , United Kingdom

Beatson WJSCC

Glasgow, , United Kingdom

Guy's & St Thomas' NHS Foundation Trust

London, , United Kingdom

The Royal Marsden Hospital

London, , United Kingdom

The Royal Marsden Hospital

Sutton, , United Kingdom

Countries

United States; Belgium; Czechia; France; Italy; Russia; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS202202_0002

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

https://www.clinicaltrials.targeting-met.com/en

Targeting MET Clinical Trial Program

Other Identifiers

2020-001776-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS202202_0002

Identifier Type: -

Identifier Source: org_study_id