BRAF V600E-mutant Metastatic Colorectal Cancer
Conditions
Keywords
Metastatic Colorectal Cancer
Brief summary
The purpose of this study is to evaluate the efficacy and safety of the combination of study drugs encorafenib, binimetinib and cetuximab in patients who have BRAF V600 mutant metastatic colorectal cancer and have not received any prior treatment for their metastatic disease.
Detailed description
The presence of a BRAFV600E mutation is considered a marker of poor prognosis in subjects with mCRC. The preclinical results and preliminary clinical data together justify the evaluation of this triple combination in the first-line setting of this population. The primary objective of the study is to evaluate the antitumor activity of the combination of encorafenib, binimetinib and cetuximab by assessing the overall response rate in adult subjects with previously untreated BRAFV600E-mutant metastatic colorectal cancer. It will also assess the effect of the triple combination on the duration of response, time to response, progression-free survival and overall survival and assess the effect on quality of life. It will also characterize the safety and tolerability of the triple combination as well as describe the pharmacokinetics (PK) of encorafenib, binimetinib, and cetuximab.
Interventions
DRUGencorafenib
300 mg administered orally once daily (QD)
DRUGBinimetinib
Binimetinib 45 mg administered orally twice daily (BID)
DRUGCetuximab
Standard of care for the 28 first weeks(\*) and then every 2 weeks (\*\*) : (\*) 400 mg/m2 administered as a 120-min infusion on Cycle 1 Day 1, followed by 250 mg/m2 administered as a 60-min infusion once weekly (QW) for the first 28 weeks. (\*\*) 500 mg/m2 administered as a 120-min infusion twice weekly (Q2W) from Week 29 (Cycle 8 Day 1) onward. Following implementation of an Urgent Safety Measure on 26 Mar 2020 due to the outbreak of COVID-19 pandemic, cetuximab infusions could be administered Q2W regardless of the cycle number, after investigator's evaluation of the benefit/risk ratio for the subject, with regards to COVID-19 pandemic.
Sponsors
Pierre Fabre Medicament
Pfizer
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
All involved know the identity of the intervention assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 18 years of age * Histologically or cytologically confirmed CRC that is metastatic * Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to screening * Evidence of measurable disease as per RECIST, v1.1 * Subject able to receive cetuximab as per approved label with regards to RAS status * Eastern Cooperative Oncology Group Status (ECOG) 0 or 1 * Adequate renal, hepatic, cardiac and bone marrow functions and adequate electrolytes as per protocol * Subject able to take oral medications
Exclusion criteria
* Prior systemic therapy for metastatic disease * Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab or other anti-EGFR inhibitors * Symptomatic brain metastasis or Leptomeningeal disease * History or current evidence of Retinal Vein Occlusion (RVO) or current risk factors for RVO * History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to first dose. * Impaired cardiovascular function or clinically significant cardiovascular diseases: history of myocardial infarction or coronary disorders within 6 months prior to start of study treatment, symptomatic congestive heart failure (grade 2 or higher), past or current clinically significant arrhythmia and/or conduction disorder within 6 months prior to study treatment start * History of thromboembolic or cerebrovascular events within 6 months prior to start of study treatment * Concurrent neuromuscular disorder that is associated with potential elevation of Creatine Kinase * Known contraindication to cetuximab administration as per SPC/approved label
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments | From initiation of treatment to disease progression up to a maximum of 17.6 months. | The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Overall Response Rate (cORR) Based on Central Tumor Assessment | From initiation of treatment to disease progression up to a maximum of 17.6 months | The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR. |
| Overall Response Rate (ORR) Based on Local Tumor Assessments | From initiation of treatment to disease progression up to a maximum of 17.6 months | The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR. |
| Overall Response Rate (ORR) Based on Central Tumor Assessments | From initiation of treatment to disease progression up to a maximum of 17.6 months | The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR. |
| Duration of Response (DOR) Per Local Assessment | From first radiographic evidence of response to disease progression up to a maximum of 17.6 months | Time from first radiographic evidence of response based on local radiologist/investigator review to the earliest documented PD or death due to underlying disease |
| Duration of Response (DOR) Per Central Assessment | From first radiographic evidence of response to disease progression up to a maximum of 17.6 months | Time from first radiographic evidence of response based on central review to the earliest documented PD or death due to underlying disease |
| Time to Response (TTR) Per Local Review | From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months | The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per local review |
| Time to Response (TTR) Per Central Review | From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months | The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per central review |
| Progression-Free Survival (PFS) Per Local Review | From initiation of treatment to disease progression or death up to a maximum of 17.6 months | Time from first dose to the earliest documented date of disease progression based on local radiologist/investigator review or death due to any cause |
| Progression of Free Survival (PFS) Per Central Review | From initiation of treatment to disease progression or death up to a maximum of 17.6 months | Time from first dose to the earliest documented date of disease progression based on central review or death due to any cause |
| Overall Survival (OS) | From initiation of treatment to death up to a maximum of 17.6 months | Time from first dose to death due to any cause |
| Change From Baseline in EORTC QLQ-C30 Over Time | From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months | The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for cancer subjects (EORTC QLQ-C30) includes a global health status/QoL. The scale ranges in score from 0 to 100, higher score on the global health status/QoL scale indicate higher QoL. Changes from baseline in EORTC QLQ-C30 global health status/quality of life (QoL) over time are presented in this record. |
| Change From Baseline in EQ-5D-5L Over Time | From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months | The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L VAS records the patient's self-rated health on a vertical visual analogue scale numbered from 0 ("The worst health you can imagine") to 100 ("The best health you can imagine"). Changes from baseline in EQ-5D-5L VAS over time are presented in this record. |
| PGIC Scores Over Time | From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months | The Patient Global Impression of Change (PGIC) is a measure of patients' perceptions of change in their symptoms over time. For this assessment, subjects answered the following question: "Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse." |
Countries
Austria, Belgium, France, Italy, Japan, Netherlands, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORIsabelle KLAUCK, MD
Corporate Medical&Patient/Consumer Division, Pierre Fabre Medicament
Participant flow
Recruitment details
95 subjects were enrolled in the study between 17 January 2019 and 27 December 2019 in 68 investigational centers : 45 in EU, 7 in UK, 10 in USA and 6 in Japan
Pre-assignment details
125 subjects were screened for inclusion in the study. 30 subjects were excluded (29 due to eligibility criteria not met and 1 due to adverse event).
Participants by arm
| Arm | Count |
|---|---|
| 1 Arm encorafenib plus binimetinib plus cetuximab
encorafenib: Once daily, orally
Binimetinib: Twice daily, orally
Cetuximab: Standard of care for the 28 first weeks and then every 2 weeks | 95 |
| Total | 95 |
Baseline characteristics
| Characteristic | 1 Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 52 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants |
| Age, Continuous | 65 years |
| Central BRAFV600E mutation result Indeterminate | 1 Participants |
| Central BRAFV600E mutation result Negative | 2 Participants |
| Central BRAFV600E mutation result Positive | 92 Participants |
| ECOG Performance Status 0 | 43 Participants |
| ECOG Performance Status 1 | 52 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Local BRAFV600E mutation result Negative | 0 Participants |
| Local BRAFV600E mutation result Positive | 95 Participants |
| Metastatic organs Adrenal gland | 3 Participants |
| Metastatic organs Bone | 4 Participants |
| Metastatic organs Liver | 52 Participants |
| Metastatic organs Lung | 35 Participants |
| Metastatic organs Lymph node | 49 Participants |
| Metastatic organs Mediastinum | 4 Participants |
| Metastatic organs Other | 11 Participants |
| Metastatic organs Ovary | 3 Participants |
| Metastatic organs Peritoneum/Omentum | 46 Participants |
| Metastatic organs Pleural cavity | 3 Participants |
| Metastatic organs Rectum | 1 Participants |
| Metastatic organs Skin | 1 Participants |
| Metastatic organs Stomach | 2 Participants |
| Number of metastatic organs 1 | 23 Participants |
| Number of metastatic organs 2 | 33 Participants |
| Number of metastatic organs >2 | 39 Participants |
| Primary tumor location Left-sided/rectum | 37 Participants |
| Primary tumor location Other | 1 Participants |
| Primary tumor location Right-sided/transverse | 57 Participants |
| Prior antineoplastic monotherapy / combination 5-Fluorouracil + Folinic Acid | 4 Participants |
| Prior antineoplastic monotherapy / combination 5-Fluorouracil + Folinic Acid + Oxaliplatin | 9 Participants |
| Prior antineoplastic monotherapy / combination Capecitabine | 6 Participants |
| Prior antineoplastic monotherapy / combination Oxaliplatin + Capecitabine | 5 Participants |
| Prior antineoplastic therapy setting Adjuvant | 17 Participants |
| Prior antineoplastic therapy setting Locally advanced | 2 Participants |
| Prior antineoplastic therapy setting Neo-adjuvant | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 71 Participants |
| Region of Enrollment Austria | 1 Participants |
| Region of Enrollment Belgium | 9 Participants |
| Region of Enrollment France | 13 Participants |
| Region of Enrollment Italy | 15 Participants |
| Region of Enrollment Japan | 11 Participants |
| Region of Enrollment Netherlands | 1 Participants |
| Region of Enrollment Spain | 29 Participants |
| Region of Enrollment United Kingdom | 13 Participants |
| Region of Enrollment United States | 3 Participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 27 / 95 |
| other Total, other adverse events | 93 / 95 |
| serious Total, serious adverse events | 49 / 95 |
Outcome results
Primary
Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments
The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.
Time frame: From initiation of treatment to disease progression up to a maximum of 17.6 months.
Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Arm | Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments | 47.8 percentage of confirmed responses |
Comparison: The null hypothesis that the true response rate is 30% will be tested against a one-sided alternative.~The cORR will be provided with a corresponding Clopper-Pearson (exact) binomial 95% CI for the Efficacy Set.~This design yields a 1-sided type I error rate equal to 1.6% and power of 80% when the true response rate is 45%.
Secondary
Change From Baseline in EORTC QLQ-C30 Over Time
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for cancer subjects (EORTC QLQ-C30) includes a global health status/QoL. The scale ranges in score from 0 to 100, higher score on the global health status/QoL scale indicate higher QoL. Changes from baseline in EORTC QLQ-C30 global health status/quality of life (QoL) over time are presented in this record.
Time frame: From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months
Population: Changes from baseline are shown up to Cycle 10 Day 1 (C10D1) and for the 30-day safety follow-up period. Beyond C10D1, less than 10 subjects filled the questionnaire. Participants analyzed corresponds to the number of participant who completed the questionnaire the at the respective time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | C2D1 | -2.64 units on a scale | Standard Deviation 19.27 |
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | C3D1 | -0.35 units on a scale | Standard Deviation 20.866 |
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | C4D1 | 0.97 units on a scale | Standard Deviation 20.238 |
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | C5D1 | -0.89 units on a scale | Standard Deviation 18.026 |
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | C6D1 | -1.92 units on a scale | Standard Deviation 22.544 |
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | C7D1 | -5.39 units on a scale | Standard Deviation 22.834 |
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | C8D1 | -4.63 units on a scale | Standard Deviation 21.225 |
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | C9D1 | -1.85 units on a scale | Standard Deviation 15.274 |
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | C10D1 | -7.69 units on a scale | Standard Deviation 17.167 |
| 1 Arm | Change From Baseline in EORTC QLQ-C30 Over Time | 30 days safety Follow up | -15.42 units on a scale | Standard Deviation 25.775 |
Secondary
Change From Baseline in EQ-5D-5L Over Time
The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L VAS records the patient's self-rated health on a vertical visual analogue scale numbered from 0 (The worst health you can imagine) to 100 (The best health you can imagine). Changes from baseline in EQ-5D-5L VAS over time are presented in this record.
Time frame: From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months
Population: Changes from baseline are shown up to Cycle 10 Day 1 (C10D1) and for the 30-day safety follow-up period. Beyond C10D1, less than 10 subjects filled the questionnaire. Participants analyzed corresponds to the number of participant who completed the questionnaire the at the respective time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | C2D1 | 0.04 units on a scale | Standard Deviation 19.707 |
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | C3D1 | 0.35 units on a scale | Standard Deviation 21.668 |
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | C4D1 | 2.66 units on a scale | Standard Deviation 19.4 |
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | C5D1 | 3.73 units on a scale | Standard Deviation 17.052 |
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | C6D1 | 1.69 units on a scale | Standard Deviation 18.421 |
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | C7D1 | 1.31 units on a scale | Standard Deviation 18.903 |
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | C8D1 | 2.89 units on a scale | Standard Deviation 15.882 |
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | C9D1 | -2.32 units on a scale | Standard Deviation 21.945 |
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | C10D1 | -4.00 units on a scale | Standard Deviation 12.503 |
| 1 Arm | Change From Baseline in EQ-5D-5L Over Time | 30 days safety Follow up | -9.35 units on a scale | Standard Deviation 23.585 |
Secondary
Confirmed Overall Response Rate (cORR) Based on Central Tumor Assessment
The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.
Time frame: From initiation of treatment to disease progression up to a maximum of 17.6 months
Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Arm | Confirmed Overall Response Rate (cORR) Based on Central Tumor Assessment | 45.7 percentage of confirmed responses |
Secondary
Duration of Response (DOR) Per Central Assessment
Time from first radiographic evidence of response based on central review to the earliest documented PD or death due to underlying disease
Time frame: From first radiographic evidence of response to disease progression up to a maximum of 17.6 months
Population: Confirmed responders per central assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Arm | Duration of Response (DOR) Per Central Assessment | 5.1 months |
Secondary
Duration of Response (DOR) Per Local Assessment
Time from first radiographic evidence of response based on local radiologist/investigator review to the earliest documented PD or death due to underlying disease
Time frame: From first radiographic evidence of response to disease progression up to a maximum of 17.6 months
Population: Confirmed responders per local radiologist/investigator assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Arm | Duration of Response (DOR) Per Local Assessment | 5.1 months |
Secondary
Overall Response Rate (ORR) Based on Central Tumor Assessments
The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.
Time frame: From initiation of treatment to disease progression up to a maximum of 17.6 months
Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Arm | Overall Response Rate (ORR) Based on Central Tumor Assessments | 60.9 percentage of responses |
Secondary
Overall Response Rate (ORR) Based on Local Tumor Assessments
The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.
Time frame: From initiation of treatment to disease progression up to a maximum of 17.6 months
Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Arm | Overall Response Rate (ORR) Based on Local Tumor Assessments | 62 percentage of responses |
Secondary
Overall Survival (OS)
Time from first dose to death due to any cause
Time frame: From initiation of treatment to death up to a maximum of 17.6 months
Population: The Full Analysis Set (FAS) is composed of all subjects having received at least one dose of study treatment (partial or full)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Arm | Overall Survival (OS) | 17.2 months |
Secondary
PGIC Scores Over Time
The Patient Global Impression of Change (PGIC) is a measure of patients' perceptions of change in their symptoms over time. For this assessment, subjects answered the following question: Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse.
Time frame: From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months
Population: PGIC scores are shown up to Cycle 10 Day 1 (C10D1) and for the 30-day safety follow-up period. Beyond C10D1, less than 10 subjects filled the questionnaire. Participants analyzed corresponds to the number of participant who completed the questionnaire the at the respective time point.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 1 Arm | PGIC Scores Over Time | C10D1 | Very much improved | 2 Participants |
| 1 Arm | PGIC Scores Over Time | C10D1 | Much improved | 4 Participants |
| 1 Arm | PGIC Scores Over Time | C10D1 | Minimally improved | 4 Participants |
| 1 Arm | PGIC Scores Over Time | C10D1 | No change | 4 Participants |
| 1 Arm | PGIC Scores Over Time | C10D1 | Minimally worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C10D1 | Much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C10D1 | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C10D1 | Missing, not done | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C9D1 | Minimally worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C2D1 | Very much improved | 5 Participants |
| 1 Arm | PGIC Scores Over Time | C2D1 | Much improved | 15 Participants |
| 1 Arm | PGIC Scores Over Time | C2D1 | Minimally improved | 17 Participants |
| 1 Arm | PGIC Scores Over Time | C2D1 | No change | 29 Participants |
| 1 Arm | PGIC Scores Over Time | C9D1 | Much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C2D1 | Minimally worse | 3 Participants |
| 1 Arm | PGIC Scores Over Time | C2D1 | Much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C2D1 | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C2D1 | Missing, not done | 22 Participants |
| 1 Arm | PGIC Scores Over Time | C3D1 | Very much improved | 10 Participants |
| 1 Arm | PGIC Scores Over Time | C3D1 | Much improved | 28 Participants |
| 1 Arm | PGIC Scores Over Time | C3D1 | Minimally improved | 11 Participants |
| 1 Arm | PGIC Scores Over Time | C3D1 | No change | 20 Participants |
| 1 Arm | PGIC Scores Over Time | C9D1 | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C3D1 | Minimally worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C3D1 | Much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C3D1 | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C3D1 | Missing, not done | 12 Participants |
| 1 Arm | PGIC Scores Over Time | C4D1 | Very much improved | 9 Participants |
| 1 Arm | PGIC Scores Over Time | C4D1 | Much improved | 31 Participants |
| 1 Arm | PGIC Scores Over Time | C4D1 | Minimally improved | 12 Participants |
| 1 Arm | PGIC Scores Over Time | C4D1 | No change | 16 Participants |
| 1 Arm | PGIC Scores Over Time | C4D1 | Minimally worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C4D1 | Much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C4D1 | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C4D1 | Missing, not done | 9 Participants |
| 1 Arm | PGIC Scores Over Time | C5D1 | Very much improved | 10 Participants |
| 1 Arm | PGIC Scores Over Time | C5D1 | Much improved | 19 Participants |
| 1 Arm | PGIC Scores Over Time | C5D1 | Minimally improved | 11 Participants |
| 1 Arm | PGIC Scores Over Time | C5D1 | No change | 13 Participants |
| 1 Arm | PGIC Scores Over Time | C5D1 | Minimally worse | 2 Participants |
| 1 Arm | PGIC Scores Over Time | C5D1 | Much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C9D1 | Missing, not done | 3 Participants |
| 1 Arm | PGIC Scores Over Time | C5D1 | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C5D1 | Missing, not done | 10 Participants |
| 1 Arm | PGIC Scores Over Time | C6D1 | Very much improved | 7 Participants |
| 1 Arm | PGIC Scores Over Time | C6D1 | Much improved | 18 Participants |
| 1 Arm | PGIC Scores Over Time | C6D1 | Minimally improved | 13 Participants |
| 1 Arm | PGIC Scores Over Time | C6D1 | No change | 13 Participants |
| 1 Arm | PGIC Scores Over Time | C6D1 | Minimally worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C6D1 | Much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C6D1 | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C6D1 | Missing, not done | 6 Participants |
| 1 Arm | PGIC Scores Over Time | C7D1 | Very much improved | 4 Participants |
| 1 Arm | PGIC Scores Over Time | C7D1 | Much improved | 13 Participants |
| 1 Arm | PGIC Scores Over Time | C7D1 | Minimally improved | 7 Participants |
| 1 Arm | PGIC Scores Over Time | C7D1 | No change | 11 Participants |
| 1 Arm | PGIC Scores Over Time | C7D1 | Minimally worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C7D1 | Much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C7D1 | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C7D1 | Missing, not done | 8 Participants |
| 1 Arm | PGIC Scores Over Time | C8D1 | Very much improved | 4 Participants |
| 1 Arm | PGIC Scores Over Time | C8D1 | Much improved | 11 Participants |
| 1 Arm | PGIC Scores Over Time | C8D1 | Minimally improved | 5 Participants |
| 1 Arm | PGIC Scores Over Time | C8D1 | No change | 5 Participants |
| 1 Arm | PGIC Scores Over Time | C8D1 | Minimally worse | 2 Participants |
| 1 Arm | PGIC Scores Over Time | C8D1 | Much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C8D1 | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | C8D1 | Missing, not done | 6 Participants |
| 1 Arm | PGIC Scores Over Time | C9D1 | Very much improved | 1 Participants |
| 1 Arm | PGIC Scores Over Time | C9D1 | Much improved | 9 Participants |
| 1 Arm | PGIC Scores Over Time | C9D1 | Minimally improved | 2 Participants |
| 1 Arm | PGIC Scores Over Time | C9D1 | No change | 5 Participants |
| 1 Arm | PGIC Scores Over Time | 30 days safety Follow-up | Very much improved | 3 Participants |
| 1 Arm | PGIC Scores Over Time | 30 days safety Follow-up | Much improved | 12 Participants |
| 1 Arm | PGIC Scores Over Time | 30 days safety Follow-up | Minimally improved | 5 Participants |
| 1 Arm | PGIC Scores Over Time | 30 days safety Follow-up | No change | 9 Participants |
| 1 Arm | PGIC Scores Over Time | 30 days safety Follow-up | Minimally worse | 6 Participants |
| 1 Arm | PGIC Scores Over Time | 30 days safety Follow-up | Much worse | 6 Participants |
| 1 Arm | PGIC Scores Over Time | 30 days safety Follow-up | Very much worse | 0 Participants |
| 1 Arm | PGIC Scores Over Time | 30 days safety Follow-up | Missing, not done | 31 Participants |
Secondary
Plasma Concentration of Binimetinib
Plasma concentration of binimetinib
Time frame: 2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days)
Secondary
Plasma Concentration of Cetuximab
Plasma concentration of cetuximab
Time frame: 2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days)
Secondary
Plasma Concentration of Encorafenib
Plasma concentration of encorafenib
Time frame: 2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days)
Secondary
Progression-Free Survival (PFS) Per Local Review
Time from first dose to the earliest documented date of disease progression based on local radiologist/investigator review or death due to any cause
Time frame: From initiation of treatment to disease progression or death up to a maximum of 17.6 months
Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Arm | Progression-Free Survival (PFS) Per Local Review | 5.8 months |
Secondary
Progression of Free Survival (PFS) Per Central Review
Time from first dose to the earliest documented date of disease progression based on central review or death due to any cause
Time frame: From initiation of treatment to disease progression or death up to a maximum of 17.6 months
Population: The Efficacy Set (ES) is composed of all included subjects having received at least one dose of study treatment (partial or full) with a centrally confirmed BRAFV600E mutation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Arm | Progression of Free Survival (PFS) Per Central Review | 5.0 months |
Secondary
Time to Response (TTR) Per Central Review
The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per central review
Time frame: From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months
Population: Confirmed responders per central assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Arm | Time to Response (TTR) Per Central Review | 1.4 months |
Secondary
Time to Response (TTR) Per Local Review
The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per local review
Time frame: From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months
Population: Confirmed responders per local radiologist/investigator assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Arm | Time to Response (TTR) Per Local Review | 1.4 months |