Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion

Description

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.

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)

Keywords

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

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join 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
  • Other protocol defined exclusion criteria could apply

Locations

  • University of California, Los Angeles (UCLA)
    Santa Monica California 90404 United States
  • Moores Cancer Center
    La Jolla California 92093 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
EMD Serono Research & Development Institute, Inc.
Links
Trial Awareness and Transparency website US Medical Information website, Medical Resources Targeting MET Clinical Trial Program
ID
NCT04515394
Phase
Phase 2
Study Type
Interventional
Last Updated