Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Cetuximab

Immunoglobulins

Mitogens

Panitumumab

Tepotinib

Antineoplastic Agents, Immunological

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.

Medical Responsible

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

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)

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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Merck KGaA, Darmstadt, Germany

EMD Serono Research & Development Institute, Inc.

Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.

Participants received Tepotinib film-coated tablets at a dose of 500 milligrams (mg) orally, once daily (QD) in combination with 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.

Tepotinib + Cetuximab

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Communication Center

DLT analysis set: all participants treated in the safety run-in period who received at least 75% of the tepotinib and cetuximab planned dose and completed the DLT period (3 weeks after start of treatment with study intervention), or who experienced a DLT during the DLT period regardless of the received amount of each study intervention.

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

Full analysis set (FAS) included all participants who were administered at least one dose of any study intervention.

Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators

None of the participants showed objective response.

Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator

FAS included all participants who were administered at least one dose of any study intervention.

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators

Overall Survival (OS) Assessed by Investigators

TEAEs

Treatment-related TEAEs

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs

SAF included all participants who were administered at least one dose of any study intervention.

Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters

Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings

Immunogenicity analysis set included all participants who received at least one dose of study intervention and had at least one valid antidrug antibody (ADA) result.

Spots Global Cancer Trial Database for hepatocyte growth factor