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

NCT04515394 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: MS202202_00022020-001776-15
• Study Type: interventional
• Target: 3
• Locations: 8 countries
• Sites: 65

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 5.0

  DLTs are defined as any of the following toxicities and judged by Investigator and/ Sponsor to be not attributable to the disease/disease-related processes under investigation: Grade 4 neutropenia for more than 7 days; Grade greater than or equal to \[\>=\] 3 febrile neutropenia with absolute neutrophil count \< 1000 per cube millimeter (per mm\^3) and a single temperature of \> 38.3 degree Celsius/a sustained temperature of \>= 38 degree Celsius for more than 1 hour; Grade 4/Grade 3 thrombocytopenia with non-traumatic bleeding; Grade 3 uncontrolled nausea/vomiting and/diarrhea that has not improved within 72 hours despite adequate and optimal treatment; Grade 4 vomiting and/diarrhea; Grade \>= 3 skin toxicity that has not resolved to Grade 2 after 14 days of adequate treatment; Any other Grade \>= 3 non-hematological AE will be defined as DLT. Exceptions are alopecia/an isolated lipase and/amylase elevation of Grade \>= 3 without clinical/radiological evidence of pancreatitis.

  Day 1 to Day 21 of Cycle 1 (each cycle is of 21 days)

• Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators

  OR is defined as a best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all target lesions.

  Time from first study treatment assessed up to 218 days

Secondary Outcomes (8)

• Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator

  Time from the first dose of study drug until occurrence of PD, death due to any cause or last tumor assessment (assessed up to 218 days)

• Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators

  Time from the first dose of study drug until occurrence of PD, death due to any cause or last tumor assessment (assessed up to 218 days)

• Overall Survival (OS) Assessed by Investigators

  Time from first study treatment until death, assessed up to 218 days

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs

  Time from first study treatment up to 30 days after the last dose, assessed up to 226 days

• Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

  Time from first study treatment up to 30 days after the last dose, assessed up to 226 days

Study Arms (1)

Tepotinib + Cetuximab

EXPERIMENTAL

Drug: Tepotinib; Biological: Cetuximab

Interventions

Tepotinib 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.

Also known as: MSC2156119J

Tepotinib + Cetuximab

Cetuximab 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.

Also known as: Erbitux®, MSB0010442D

Tepotinib + Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (65)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California, Los Angeles (UCLA)

Santa Monica, California, 90404, United States

Location

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic Hospital

Jacksonville, Florida, 322224-1865, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214-3728, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

North Shore-LIJ Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Allegheny-Singer Research Institute

Pittsburgh, Pennsylvania, 15212, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Scott & White Vasicek Cancer Treatment Center

Temple, Texas, 76508-0001, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109-1023, United States

Location

Aurora Cancer Care - Milwaukee West

Wauwatosa, Wisconsin, 53226, United States

Location

Antwerp University Hospital

Antwerp, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Universtity Hospital Brno

Brno, Czechia

Location

University Hospital Olomouc

Olomouc, Czechia

Location

Dept. of Oncology Faculty Hospital Motol

Prague, Czechia

Location

Hospital Na Bulovce

Prague, Czechia

Location

CHU Besançon Hôpital Jean Minjoz

Besançon, France

Location

University Hospital of Besançon

Besançon, France

Location

CHU Estaing

Clermont-Ferrand, France

Location

CHU Hôpital Henri Mondor

Créteil, France

Location

Clinique Victor Hugo

Le Mans, France

Location

CHU de Poitiers

Poitiers, France

Location

Curie Institute

Saint-Cloud, France

Location

Institut Curie - René-Huguenin Hospital

Saint-Cloud, France

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura die Tumori

Meldona, Italy

Location

Fondazione IRCCS - Istituto Tumori Milano

Milan, Italy

Location

Grande Ospedale Metropolitano Niguarda

Milan, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Istituto Nazionale Tumori, Fondazione G. Pascale Napoli

Napoli, Italy

Location

UOC Oncoematologia AOU Vanvitelli

Napoli, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, Italy

Location

Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chiara

Pisa, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Rome, Italy

Location

Foundation IRCCS Casa Sollievo della Sofferenza

San Giovanni Rotondo FG, Italy

Location

Arkangelsk Clinical Oncological Dyspensary

Arkhangelsk, Russia

Location

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

Chelyabinsk, Russia

Location

Kursk Regional Clinical Oncology Dispensary

Kislino, Russia

Location

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

Moscow, Russia

Location

Limited Liability Company Medicine 24/7

Moscow, Russia

Location

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

Moscow, Russia

Location

Omsk Regional Oncology Dispensary

Omsk, Russia

Location

LLC Clinica UZI 4D

Pyatigorsk, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, Russia

Location

Tomsk National Research Medical Center

Tomsk, Russia

Location

MKMC Medical City

Tyumen, Russia

Location

SAHI Republican Clinical Oncology Dispensary

Ufa, Russia

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

VHIO Valle de Hebron Instituto de Oncologia

Barcelona, Spain

Location

H.U. Ramon y Cajal

Madrid, Spain

Location

HM-CIOCC

Madrid, Spain

Location

Hospital de Madrid Norte Sanchinarro

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital UNiversitario La Paz

Madrid, Spain

Location

H.U.Marqués de Valdecilla

Santander, Spain

Location

HUVirgen del Rocio

Seville, Spain

Location

Consorcio Hospital General Universitario de Valencia

Valencia, Spain

Location

Bristol Oncology Centre

Bristol, United Kingdom

Location

Beatson WJSCC

Glasgow, United Kingdom

Location

Guy's & St Thomas' NHS Foundation Trust

London, United Kingdom

Location

The Royal Marsden Hospital

London, United Kingdom

Location

The Royal Marsden Hospital

Sutton, United Kingdom

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources
• Targeting MET Clinical Trial Program

MeSH Terms

Conditions

Colorectal Neoplasms; Deafness, Autosomal Recessive 39

Interventions

tepotinib; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 17, 2020
• Study Start: January 28, 2021
• Primary Completion: March 14, 2022
• Study Completion: March 31, 2022
• Last Updated: December 22, 2022
• Results First Posted: December 22, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

Locations

ES (11); IT (10); GB (5); CZ (4); RU (12); US (13); FR (8); BE (2)