Study of Tepotinib Combined With Cetuximab in Participants With Left-Sided RAS/BRAF Wild Type Metastatic Colorectal Cancer (PERSPECTIVE)
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Tepotinib; Cetuximab
Intervention description: 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.; 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 MeSH terms: Cetuximab; Tepotinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal cancer; RAS wild-type; Tepotinib; Cetuximab; Erbitux; Epidermal growth factor receptor resistance; Hepatocyte growth factor; Panitumumab; Mesenchymal epithelial transition

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