Clinical Trials /

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

NCT04515394

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Tepotinib Combined With Cetuximab in Participants Left-Sided Metastatic Colorectal Cancer (mCRC) Acquired Resistance Due to Mesenchymal Epithelial Transition (MET) Amplification
  • Official Title: A Phase II Single-Arm Study to Investigate Tepotinib Combined With Cetuximab in RAS/BRAF Wild-Type Left-Sided Metastatic Colorectal Cancer (mCRC) Patients Having Acquired Resistance to Anti-EGFR Antibody Targeting Therapy Due to MET Amplification

Clinical Trial IDs

  • ORG STUDY ID: MS202202_0002
  • SECONDARY ID: 2020-001776-15
  • NCT ID: NCT04515394

Conditions

  • Colorectal Neoplasms

Interventions

DrugSynonymsArms
TepotinibMSC2156119JTepotinib + Cetuximab
CetuximabErbitux®, MSB0010442DTepotinib + Cetuximab

Purpose

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 mCRC having acquired resistance to anti-epidermal growth factor receptor (EGFR) antibody targeted therapy due to mesenchymal epithelial transition (MET) amplification.

Trial Arms

NameTypeDescriptionInterventions
Tepotinib + CetuximabExperimental
  • Tepotinib
  • Cetuximab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Time Frame:Day 1 to Day 21 of Cycle 1 (each cycle is of 21 days)
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

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

Last Updated

August 13, 2020