Clinical trial NCT04515394: Study of Tepotinib Combined With Cetuximab in Participants With Left-Sided RAS/BRAF Wild Type Metastatic Colorectal Cancer (PERSPECTIVE)
Official title: A Phase II Single-Arm Study to Investigate Tepotinib Combined With Cetuximab in RAS/BRAF Wild-Type Left-Sided mCRC Patients Having Acquired Resistance to Anti-EGFR Antibody Targeting Therapy Due to MET Amplification (PERSPECTIVE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Keywords: Colorectal cancer
RAS wild-type
Tepotinib
Cetuximab
Erbitux
Epidermal growth factor receptor resistance
Hepatocyte growth factor
Panitumumab
Mesenchymal epithelial transition
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2020-08-17
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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
* Other protocol defined inclusion criteria could apply

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
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: 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
timeFrame: Day 1 to Day 21 of Cycle 1 (each cycle is of 21 days)
measure: Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators
timeFrame: Time from first study treatment assessed up to 218 days
Secondary outcomes:
measure: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator
timeFrame: 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)
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators
timeFrame: 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)
measure: Overall Survival (OS) Assessed by Investigators
timeFrame: Time from first study treatment until death, assessed up to 218 days
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs
timeFrame: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
timeFrame: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
timeFrame: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days
measure: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
timeFrame: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days
measure: Number of Participants With At Least 1 Postive Anti-Drug Antibodies (ADAs) for Cetuximab
timeFrame: At Day 1 of cycle 1 (each cycle is of 21 days) and at End of Treatment (14 days after last dose, assessed up to 210 days)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: La Jolla
country: United States
facility: Moores Cancer Center
state: California
city: Santa Monica
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Washington
country: United States
facility: Georgetown Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital
state: Florida
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Lake Success
country: United States
facility: North Shore-LIJ Monter Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: Allegheny-Singer Research Institute
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Temple
country: United States
facility: Scott & White Vasicek Cancer Treatment Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Wauwatosa
country: United States
facility: Aurora Cancer Care - Milwaukee West
state: Wisconsin
city: Antwerp
country: Belgium
facility: Antwerp University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Brno
country: Czechia
facility: Universtity Hospital Brno
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Prague
country: Czechia
facility: Dept. of Oncology Faculty Hospital Motol
city: Prague
country: Czechia
facility: Hospital Na Bulovce
city: Besancon Cedex
country: France
facility: CHU Besançon Hôpital Jean Minjoz
city: Besançon
country: France
facility: University Hospital of Besançon
city: Clermont Ferrand Cedex 1
country: France
facility: CHU Estaing
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Créteil
country: France
facility: CHU Hôpital Henri Mondor
city: Le Mans Cedex 02
country: France
facility: Clinique Victor Hugo
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Poitiers
country: France
facility: CHU de Poitiers
city: Saint Cloud
country: France
facility: Curie Institute
city: Saint-Cloud
country: France
facility: Institut Curie - René-Huguenin Hospital
city: Meldona
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura die Tumori
city: Milan
country: Italy
facility: Fondazione IRCCS - Istituto Tumori Milano
city: Milan
country: Italy
facility: Grande Ospedale Metropolitano Niguarda
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori, Fondazione G. Pascale Napoli
city: Napoli
country: Italy
facility: UOC Oncoematologia AOU Vanvitelli
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chiara
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: San Giovanni Rotondo FG
country: Italy
facility: Foundation IRCCS Casa Sollievo della Sofferenza
city: Arkhangelsk
country: Russian Federation
facility: Arkangelsk Clinical Oncological Dyspensary
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
city: Kislino
country: Russian Federation
facility: Kursk Regional Clinical Oncology Dispensary
city: Moscow
country: Russian Federation
facility: FSBI "National Medical Research Center of Oncology n.a. N.N. Blokhina" of the MoH of the RF
city: Moscow
country: Russian Federation
facility: Limited Liability Company Medicine 24/7
city: Moscow
country: Russian Federation
facility: Russian Cancer research center n.a. N.N. Blokhin
city: Omsk
country: Russian Federation
facility: Omsk Regional Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: LLC Clinica UZI 4D
city: St. Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
city: Tomsk
country: Russian Federation
facility: Tomsk National Research Medical Center
city: Tyumen
country: Russian Federation
facility: MKMC Medical City
city: Ufa
country: Russian Federation
facility: SAHI Republican Clinical Oncology Dispensary
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: VHIO Valle de Hebron Instituto de Oncologia
city: Madrid
country: Spain
facility: H.U. Ramon y Cajal
city: Madrid
country: Spain
facility: HM-CIOCC
city: Madrid
country: Spain
facility: Hospital de Madrid Norte Sanchinarro
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital UNiversitario La Paz
city: Santander
country: Spain
facility: H.U.Marqués de Valdecilla
city: Sevilla
country: Spain
facility: HUVirgen del Rocio
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario de Valencia
city: Bristol
country: United Kingdom
facility: Bristol Oncology Centre
city: Glasgow
country: United Kingdom
facility: Beatson WJSCC
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: