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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
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.
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
DLTs are defined as any of the following toxicities and judged by Investigator and/ Sponsor to be not attributable to the disease/disease-related processes under investigation: Grade 4 neutropenia for more than 7 days; Grade greater than or equal to \[\>=\] 3 febrile neutropenia with absolute neutrophil count \< 1000 per cube millimeter (per mm\^3) and a single temperature of \> 38.3 degree Celsius/a sustained temperature of \>= 38 degree Celsius for more than 1 hour; Grade 4/Grade 3 thrombocytopenia with non-traumatic bleeding; Grade 3 uncontrolled nausea/vomiting and/diarrhea that has not improved within 72 hours despite adequate and optimal treatment; Grade 4 vomiting and/diarrhea; Grade \>= 3 skin toxicity that has not resolved to Grade 2 after 14 days of adequate treatment; Any other Grade \>= 3 non-hematological AE will be defined as DLT. Exceptions are alopecia/an isolated lipase and/amylase elevation of Grade \>= 3 without clinical/radiological evidence of pancreatitis.
Time frame: 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 v1.1) Assessed by Investigators
OR is defined as a best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all target lesions.
Time frame: Time from first study treatment assessed up to 218 days
Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator
For participants with objective response, DoR is the time from when the complete response (CR) or partial response (PR) (whichever is first) criteria are first met until progression disease (PD) or death due to any cause within the period of 2 scheduled tumor assessments (84 or 168 days) after the last tumor assessment, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
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Mayo Clinic
Phoenix, Arizona, United States
Moores Cancer Center
La Jolla, California, United States
University of California, Los Angeles (UCLA)
Santa Monica, California, United States
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, United States
Mayo Clinic Hospital
Jacksonville, Florida, United States
Cancer Center of Kansas
Wichita, Kansas, United States
Mayo Clinic
Rochester, Minnesota, United States
North Shore-LIJ Monter Cancer Center
Lake Success, New York, United States
Allegheny-Singer Research Institute
Pittsburgh, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
...and 55 more locations
Time frame: 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)
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators
PFS is defined as the time (in months) from first administration of study intervention to the date of the first documentation of progression disease (PD) or death due to any cause within the period of 2 scheduled tumor assessments (84 or 168 days) after the last tumor assessment, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was to be estimated using Kaplan-Meier (KM) plots.
Time frame: 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)
Overall Survival (OS) Assessed by Investigators
OS is defined as the time (in months) from first administration of study intervention to the date of death. OS was to be estimated using Kaplan-Meier (KM) plots.
Time frame: Time from first study treatment until death, assessed up to 218 days
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events that started or worsened after first dose of study intervention until 30 days after last dose. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention.
Time frame: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Vital sign assessment included assessments of height, weight, temperature, pulse rate, respiratory rate, and blood pressure. Clinical significance was determined by the investigator. Number of participants who had any clinically significant changes from baseline in vital signs were reported.
Time frame: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Laboratory investigation included hematology, biochemistry, coagulation, routine urinalysis and other screening tests (Follicle-stimulating hormone (FSH) and estradiol, Serum or highly sensitive urine human chorionic gonadotropin (hCG) pregnancy test, Serology (HIV antibody, hepatitis B surface antigen \[HBsAg\], and hepatitis C virus antibody) and all of the safety labs were performed locally. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.
Time frame: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days
Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
12-lead ECG recordings included heart rate and measures PR, QRS, QT and QTcF intervals. 12-lead ECG recordings were obtained after the participants have rested for at least 5 minutes in semi-supine or supine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
Time frame: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days
Number of Participants With At Least 1 Postive Anti-Drug Antibodies (ADAs) for Cetuximab
Serum samples were analyzed by a validated electrochemiluminescence immunoassay method to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.
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 210 days)