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

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT04515394

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

Enrollment

Locations

Arm

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is 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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms	Drug: Tepotinib Biological: Cetuximab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jan 28, 2021

Actual Primary Completion Date :

Mar 14, 2022

Actual Study Completion Date :

Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tepotinib + Cetuximab	Drug: Tepotinib Participants will receive Tepotinib initially at 500 milligrams (mg) once daily (QD) (2 film coated tablets of 250 mg QD). For potential dose de-escalation, the available 250 mg dose strength will be used (1 tablet once daily) 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. Other Names: MSC2156119J Biological: Cetuximab Cetuximab, is administered at an initial dose of 400 milligrams per square meter (mg/m^2) body surface area, over a recommended intravenous infusion period of 120 minutes and a maximum infusion rate of 5 milligrams per minute (5 mg/min), followed by or starting with weekly infusions at a dose of 250 mg/m^2 over a recommended infusion period of 60 minutes and a maximum infusion rate of 10 mg/min until disease progression, death, Adverse event (AE) leading to discontinuation of both study interventions, study withdrawal, or withdrawal of consent, whichever occurs first. Other Names: Erbitux® MSB0010442D

Arm

Intervention/Treatment

Experimental: Tepotinib + Cetuximab

Drug: Tepotinib

Participants will receive Tepotinib initially at 500 milligrams (mg) once daily (QD) (2 film coated tablets of 250 mg QD). For potential dose de-escalation, the available 250 mg dose strength will be used (1 tablet once daily) 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.

Other Names:

MSC2156119J

Biological: Cetuximab

Cetuximab, is administered at an initial dose of 400 milligrams per square meter (mg/m^2) body surface area, over a recommended intravenous infusion period of 120 minutes and a maximum infusion rate of 5 milligrams per minute (5 mg/min), followed by or starting with weekly infusions at a dose of 250 mg/m^2 over a recommended infusion period of 60 minutes and a maximum infusion rate of 10 mg/min until disease progression, death, Adverse event (AE) leading to discontinuation of both study interventions, study withdrawal, or withdrawal of consent, whichever occurs first.

Other Names:

Erbitux®

MSB0010442D

Outcome Measures

Primary Outcome Measures

Number of Participants Experiencing Dose Limiting Toxicities (DLTs) According to National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) for Adverse Events (AEs) Version 5.0 [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 v 1.1) Assessed by Investigators [Time from first study treatment assessed up to 556 days]

Secondary Outcome Measures

Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) Assessed by Investigators [Time from first study treatment assessed up to 556 days]
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) Assessed by Investigators [Time from first study treatment assessed up to 556 days]
Overall Survival (OS) Assessed by Investigators [Time from first study treatment assessed up to 556 days]
Number of Participants with Adverse Events (AEs) and Treatment Related Adverse Events (TRAEs) [Time from first study treatment up to 30 days after the last dose, assessed up to 221 days]
Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings [Time from first study treatment up to 30 days after the last dose, assessed up to 221 days]
Number of participants with clinically significant changes in vital signs, laboratory parameters and 12-lead ECG will be reported.
Number of Participants With Anti-Drug Antibodies (ADAs) for Cetuximab [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 205 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85054
2	Moores Cancer Center	La Jolla	California	United States	92093
3	University of California, Los Angeles (UCLA)	Santa Monica	California	United States	90404
4	Georgetown Lombardi Comprehensive Cancer Center	Washington	District of Columbia	United States	20007
5	Mayo Clinic Hospital	Jacksonville	Florida	United States	322224-1865
6	Cancer Center of Kansas	Wichita	Kansas	United States	67214-3728
7	Mayo Clinic	Rochester	Minnesota	United States	55905
8	North Shore-LIJ Monter Cancer Center	Lake Success	New York	United States	11042
9	Allegheny-Singer Research Institute	Pittsburgh	Pennsylvania	United States	15212
10	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
11	Scott & White Vasicek Cancer Treatment Center	Temple	Texas	United States	76508-0001
12	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109-1023
13	Aurora Cancer Care - Milwaukee West	Wauwatosa	Wisconsin	United States	53226
14	Antwerp University Hospital	Antwerp		Belgium
15	UZ Leuven	Leuven		Belgium
16	Universtity Hospital Brno	Brno		Czechia
17	University Hospital Olomouc	Olomouc		Czechia
18	Dept. of Oncology Faculty Hospital Motol	Prague		Czechia
19	Hospital Na Bulovce	Prague		Czechia
20	CHU Besançon Hôpital Jean Minjoz	Besancon Cedex		France
21	University Hospital of Besançon	Besançon		France
22	CHU Estaing	Clermont Ferrand Cedex 1		France
23	CHU Estaing	Clermont-Ferrand		France
24	CHU Hôpital Henri Mondor	Créteil		France
25	Clinique Victor Hugo	Le Mans Cedex 02		France
26	Clinique Victor Hugo	Le Mans		France
27	CHU de Poitiers	Poitiers		France
28	Curie Institute	Saint Cloud		France
29	Institut Curie - René-Huguenin Hospital	Saint-Cloud		France
30	Istituto Scientifico Romagnolo per lo Studio e la Cura die Tumori	Meldona		Italy
31	Fondazione IRCCS - Istituto Tumori Milano	Milan		Italy
32	Grande Ospedale Metropolitano Niguarda	Milan		Italy
33	Istituto Europeo di Oncologia	Milan		Italy
34	Istituto Nazionale Tumori, Fondazione G. Pascale Napoli	Napoli		Italy
35	UOC Oncoematologia AOU Vanvitelli	Napoli		Italy
36	Istituto Oncologico Veneto IRCCS	Padova		Italy
37	Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chiara	Pisa		Italy
38	Fondazione Policlinico Universitario Agostino Gemelli	Rome		Italy
39	Foundation IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo FG		Italy
40	Arkangelsk Clinical Oncological Dyspensary	Arkhangelsk		Russian Federation
41	Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine	Chelyabinsk		Russian Federation
42	Kursk Regional Clinical Oncology Dispensary	Kislino		Russian Federation
43	FSBI "National Medical Research Center of Oncology n.a. N.N. Blokhina" of the MoH of the RF	Moscow		Russian Federation
44	Limited Liability Company Medicine 24/7	Moscow		Russian Federation
45	Russian Cancer research center n.a. N.N. Blokhin	Moscow		Russian Federation
46	Omsk Regional Oncology Dispensary	Omsk		Russian Federation
47	LLC Clinica UZI 4D	Pyatigorsk		Russian Federation
48	Pavlov First Saint Petersburg State Medical University	St. Petersburg		Russian Federation
49	Tomsk National Research Medical Center	Tomsk		Russian Federation
50	MKMC Medical City	Tyumen		Russian Federation
51	SAHI Republican Clinical Oncology Dispensary	Ufa		Russian Federation
52	Hospital Clinic de Barcelona	Barcelona		Spain
53	Hospital del Mar	Barcelona		Spain
54	VHIO Valle de Hebron Instituto de Oncologia	Barcelona		Spain
55	H.U. Ramon y Cajal	Madrid		Spain
56	HM-CIOCC	Madrid		Spain
57	Hospital de Madrid Norte Sanchinarro	Madrid		Spain
58	Hospital Universitario 12 de Octubre	Madrid		Spain
59	Hospital UNiversitario La Paz	Madrid		Spain
60	H.U.Marqués de Valdecilla	Santander		Spain
61	HUVirgen del Rocio	Sevilla		Spain
62	Consorcio Hospital General Universitario de Valencia	Valencia		Spain
63	Bristol Oncology Centre	Bristol		United Kingdom
64	Beatson WJSCC	Glasgow		United Kingdom
65	Guy's & St Thomas' NHS Foundation Trust	London		United Kingdom
66	The Royal Marsden Hospital	London		United Kingdom
67	The Royal Marsden Hospital	Sutton		United Kingdom