Trial Outcomes & Findings for Study of Tepotinib Combined With Cetuximab in Participants With Left-Sided RAS/BRAF Wild Type Metastatic Colorectal Cancer (PERSPECTIVE) (NCT NCT04515394)

Last Updated: 2022-12-22

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Day 1 to Day 21 of Cycle 1 (each cycle is of 21 days)

Results posted on

2022-12-22

Participant Flow

A total of 57 participants were screened. Out of which, 3 participants were enrolled and 2 participants received treatment in this study.

Participant milestones

Participant milestones
Measure	Tepotinib + Cetuximab 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.
Overall Study STARTED	3
Overall Study Treated	2
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Tepotinib + Cetuximab 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.
Overall Study Participant did not receive treatment	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tepotinib + Cetuximab n=3 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 21 of Cycle 1 (each cycle is of 21 days)

Population: 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Cetuximab n=2 Participants 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.
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	0 Participants

PRIMARY outcome

Timeframe: Time from first study treatment assessed up to 218 days

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

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Cetuximab n=2 Participants 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.
Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators	0 Participants

SECONDARY outcome

Timeframe: 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)

Population: None of the participants showed objective response.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

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

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Cetuximab n=2 Participants 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.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators	NA months Median (and corresponding 95% CI) could not be estimated by KM estimates due to low sample size (2 participants) and low number of events of interest (1 participant).

SECONDARY outcome

Timeframe: Time from first study treatment until death, assessed up to 218 days

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

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Cetuximab n=2 Participants 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.
Overall Survival (OS) Assessed by Investigators	NA months Median (and corresponding 95% CI) could not be estimated by KM estimates as there was no event of interest (death).

SECONDARY outcome

Timeframe: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days

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

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Cetuximab n=2 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs TEAEs	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs Treatment-related TEAEs	2 Participants

SECONDARY outcome

Timeframe: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days

Population: SAF included all participants who were administered at least one dose of any 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.

Outcome measures

Outcome measures
Measure	Tepotinib + Cetuximab n=2 Participants 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.
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	0 Participants

SECONDARY outcome

Timeframe: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days

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

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Cetuximab n=2 Participants 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.
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters	0 Participants

SECONDARY outcome

Timeframe: Time from first study treatment up to 30 days after the last dose, assessed up to 226 days

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

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Cetuximab n=2 Participants 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.
Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings	0 Participants

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Tepotinib + Cetuximab n=2 Participants 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.
Number of Participants With At Least 1 Postive Anti-Drug Antibodies (ADAs) for Cetuximab	0 Participants

Adverse Events

Tepotinib + Cetuximab

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Tepotinib + Cetuximab n=2 participants at risk 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.
Skin and subcutaneous tissue disorders Skin toxicity	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Skin and subcutaneous tissue disorders Skin lesion	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
General disorders oedema peripheral	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Gastrointestinal disorders diarrhea	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
General disorders Mucosal inflammation	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Skin and subcutaneous tissue disorders drug eruption	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Infections and infestations paronychia	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Skin and subcutaneous tissue disorders dry skin	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Metabolism and nutrition disorders Hypoalbuminaemia	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Metabolism and nutrition disorders Hypocalcaemia	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Metabolism and nutrition disorders Hypomagnesaemia	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Nervous system disorders Headache	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Product Issues Device dislocation	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Metabolism and nutrition disorders Iron deficiency	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Musculoskeletal and connective tissue disorders Back pain	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Musculoskeletal and connective tissue disorders Arthralgia	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.
Investigations Weight increased	50.0% 1/2 • Time from first study treatment up to 30 days after the last dose, assessed up to 226 days Safety analysis set (SAF) included all participants who were administered at least one dose of any study intervention.

Additional Information

Communication Center

Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER