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| ID | Type | Description | Link |
|---|---|---|---|
| C4211004 | Other Identifier | Alias Study Number | |
| 2017-003464-12 | EudraCT Number |
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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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This is a multicenter, open-label, Phase 1B/2 study to evaluate the safety and assess the preliminary anti-tumor activity of binimetinib administered in combination with nivolumab or nivolumab + ipilimumab in adult patients with advanced metastatic colorectal cancer (mCRC) with microsatellite stable (MSS) disease and presence of a RAS mutation that have received at least one prior line of therapy and no more than 2 prior lines of therapy. The study contains a Phase 1b period to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) and schedule of binimetinib followed by a randomized Phase 2 period to assess the efficacy of the combinations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1b / Arm 1A | Experimental | binimetinib + nivolumab |
|
| Phase 1b / Arm 1B | Experimental | binimetinib + nivolumab + ipilimumab |
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| Phase 2 / Arm 2A | Experimental | binimetinib + nivolumab |
|
| Phase 2 / Arm 2B | Experimental | binimetinib + nivolumab + ipilimumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| binimetinib | Drug | Orally, twice daily. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT) | DLT:Adverse event(AE)/abnormal laboratory assessed unrelated-disease,disease progression,intercurrent illness/concomitant medication/therapies resulting inability tolerate 75% dose intensity in Cycle 1.Total bilirubin(TBL)grade(G)>=3 (>3.0*upper limit of normal[ULN)]);AST/ALT>5-8*ULN>5 days,>8*ULN,>3*ULN concurrent TBL>2*ULN;G>=3 serum creatinine,CK elevation,ECG QTcF prolonged,G3 troponin,electrolyte>72 hours,G3/4 amylase/lipase.G4 ANC,platelet count>7 days;G3/4 platelet count,other AE except lymphopenia.G>=3 retinopathy,other disorder>21 days;G2 uveitis/eye pain/blurred vision/decreased visual acuity;G4 other disorder.Decrease LVEF>10% G>=3 cardiac disorders.G3/4 hypertension.G3 fatigue>=7 days,hypersensitivity,infusion reaction,fever>=72 hours/hemodynamic compromise,endocrinopathy.G>=2 interstitial lung disease/pneumonitis;G3 bronchospasm.G3/4 rash,hand foot skin reaction,photosensitivity.G3 colitis;G3/4 diarrhea,nausea/vomiting.Neurologic G3.Other hematologic/nonhematolic G>=3 AE. | Cycle 1: Day 1 up to Day 28 |
| Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | ORR was defined as the percentage of participants who achieved a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<)10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was considered progression. | From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 2: maximum up to 26 months approximately) |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b: Objective Response Rate (ORR) Per RECIST v1.1 | ORR was defined as the percentage of participants who achieved a BOR of CR or PR as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
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Key Inclusion Criteria
Measurable, histologically/cytologically confirmed metastatic colorectal cancer (mCRC).
Able to provide a sufficient amount of representative tumor specimen for central laboratory testing of RAS mutation status and microsatellite stable (MSS).
Metastatic colorectal cancer (mCRC) categorized as microsatellite stable (MSS) by polymerase chain reaction (PCR) per local assay at any time prior to Screening or by the central laboratory.
RAS mutation per local assay at any time prior to Screening or by the central laboratory.
Have received at least 1 prior line of therapy and meets at least one of the following criteria:
Have received no more than 2 prior lines of therapy (maintenance therapy given in the metastatic setting will not be considered a separate regimen). Generally, treatments that are separated by an event of progression are considered different regimens.
Adequate bone marrow, cardiac, kidney and liver function
Able to take oral medications
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of child-bearing potential
Non-sterile male patients who are sexually active with female partners of childbearing potential must agree to follow instructions for acceptable or highly effective method(s) of contraception for the duration of study treatment and for 7 months after the last dose of study treatment with nivolumab
Key Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Hematology/Oncology | Los Angeles | California | 90095 | United States | ||
| UCLA Hematology/Oncology - Santa Monica |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38600471 | Derived | Elez E, Cubillo A, Alfonso PG, Middleton MR, Chau I, Alkuzweny B, Alcasid A, Zhang X, Van Cutsem E. Binimetinib in combination with nivolumab or nivolumab and ipilimumab in patients with previously treated microsatellite-stable metastatic colorectal cancer with RAS mutations in an open-label phase 1b/2 study. BMC Cancer. 2024 Apr 11;24(1):446. doi: 10.1186/s12885-024-12153-5. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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This study included 2 phases: Phase 1b and Phase 2. The recommended dose for Phase 2 (RP2D) of binimetinib was determined in Phase 1b (dose finding phase).
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1b: Nivolumab+Binimetinib | Participants with previously treated microsatellite-stable (MSS) metastatic colorectal cancer with rat sarcoma virus (RAS) mutation received binimetinib at a starting dose of 45 milligrams (mg) tablet orally twice daily (BID) along with 480 mg intravenously (IV) dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase 1b: Dose Finding Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 2, 2018 | Oct 4, 2021 |
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In phase 1 it is sequential and then in phase 2 it is parallel.
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| nivolumab | Drug | Intravenously (IV) every 4 weeks (Q4W) |
|
| ipilimumab | Drug | intravenously (IV) every 8 weeks (Q8W) |
|
| From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately) |
| Duration of Response (DOR) as Per RECIST v1.1 | DOR was defined as the time between the date of the first documented confirmed response (PR or CR) and the date of the first documented progression or death due to any cause. As per RECIST v1.1: CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures <10 mm. PR was defined as at least 30% decrease in sum of measures (tumor lesions- longest diameter and nodes- short axis) of target lesions, taking as reference baseline sum of diameters. PD was defined as at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. | From date of first documented CR/PR to date of first documented PD, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately, Phase 2: maximum up to 26 months approximately) |
| Percentage of Participants With Complete Response as Per RECIST v1.1 | Complete response as per RECIST v1.1 was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. | From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately) |
| Number of Participants With Treatment-Emergent Adverse Events (TEAE) Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 | AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs: events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy minus 1 day, whichever occurred first. TEAE graded by CTCAE grade 4.03: Grade 3: severe/medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care activities of daily living (ADL); Grade 4: life-threatening consequence, urgent intervention indicated. In this outcome measure, number of participants with 'all grades' and 'Grade 3/4' were reported. | From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately) |
| Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03: Hematology and Coagulation | Hematological parameters included: Hemoglobin graded high, Hemoglobin graded low, Platelets count graded low, White Blood Cell (WBC) graded high, WBC graded low, Neutrophils graded low, Lymphocytes graded high, Lymphocytes graded low. Coagulation parameters included: International Normalized Ratio (INR) graded high, Activated Partial Thromboplastin Time (aPTT) graded high. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported. | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
| Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Hematology and Coagulation | Hematology parameters: Basophils, Eosinophils, Hematocrit, Monocytes, Red blood cells (RBC). Coagulation parameters: Prothrombin Time. Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Laboratory parameters were graded based on laboratory normal ranges as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported. | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
| Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on CTCAE v4.03: Chemistry | Abnormalities: Albumin graded low, Alkaline phosphatase (ALP) graded high, Alanine aminotransferase (ALT) graded high, Aspartate aminotransferase (AST) graded high, Bilirubin graded high, Amylase graded high, Creatinine graded high, Corrected calcium graded high, Creatine Kinase (CK) graded high, Glucose graded high, Glucose graded low, Lipase graded high, Magnesium graded high, Magnesium graded low, Potassium graded high, Potassium graded low, Sodium graded high and Sodium graded low. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported. | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
| Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Chemistry and Thyroid Function | Chemistry laboratory parameters: Blood urea nitrogen (BUN), Total protein, Chloride, Cancer antigen 19-9 (CA 19-9), Brain natriuretic peptide (BNP), Bicarbonate, Direct bilirubin, Carcinoembryonic antigen (CEA), Lactate dehydrogenase (LDH), Uric acid, Troponin I. Thyroid panel laboratory parameters: Thyroid-stimulating hormone (TSH), Free triiodothyronine (T3), Free thyroxine (T4). Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Shift in chemistry and thyroid panel severity from baseline grade low, normal, high and missing to the post baseline grades as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported. | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
| Number of Participants With Abnormal Hepatic Laboratory Values | Criteria for abnormal hepatic laboratory parameters: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT): >3* upper limit of normal (ULN), >5*ULN, >8*ULN, >10*ULN, >20*ULN; Total bilirubin (TBL) >1.5*ULN, >2*ULN; Alkaline phosphatase (ALP) >2*ULN, >3*ULN. Categories with at least 1 non-zero data values are reported. | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
| Concentration Versus Time Summary of Plasma Concentration of Binimetinib | 1.5 hours post dose of binimetinib on Day 1, 15 of Cycle 1; pre dose of binimetinib on Day 15 of Cycle 1, 2, 3, 4, 5 |
| Santa Monica |
| California |
| 90404 |
| United States |
| Christiana Care Health Services, Helen F. Graham Cancer Center Pharmacy, Suite 3200 | Newark | Delaware | 19713 | United States |
| Christiana Care Health Services, Helen F. Graham Cancer Center | Newark | Delaware | 19713 | United States |
| Christiana Care Oncology Hematology, Helen F Graham Cancer Center, Suite 2400 | Newark | Delaware | 19713 | United States |
| Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center | Newark | Delaware | 19713 | United States |
| Christiana Care Health Services, Christiana Hospital | Newark | Delaware | 19718 | United States |
| Georgetown University Medical Center Department of Pharmacy, Research | Washington D.C. | District of Columbia | 20007 | United States |
| Georgetown University Medical Center | Washington D.C. | District of Columbia | 20007 | United States |
| Hematology Oncology Associates of the Treasure Coast | Port Saint Lucie | Florida | 34952 | United States |
| Indiana CTSI Clinical Research Center (ICRC) | Indianapolis | Indiana | 46202 | United States |
| Indiana University Health Hospital | Indianapolis | Indiana | 46202 | United States |
| Indiana University Health Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | 46202 | United States |
| Investigational Drug Services IUHSCC | Indianapolis | Indiana | 46202 | United States |
| Sidney &Lois Eskenazi Hospital | Indianapolis | Indiana | 46202 | United States |
| Spring Mill Medical Center | Indianapolis | Indiana | 46290 | United States |
| Siteman Cancer Center - Barnes St. Peters | City of Saint Peters | Missouri | 63376 | United States |
| Siteman Cancer Center - West County | Creve Coeur | Missouri | 63141 | United States |
| Siteman Cancer Center - North County | Florissant | Missouri | 63031 | United States |
| Center for Outpatient Health (Dermatology Clinic) | St Louis | Missouri | 63108 | United States |
| Center for Outpatient Health (Ophthalmology Clinic) | St Louis | Missouri | 63108 | United States |
| Barnes-Jewish Hospital | St Louis | Missouri | 63110 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Siteman Cancer Center - South County | St Louis | Missouri | 63129 | United States |
| Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Investigational Drug Service of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| Sarah Cannon Research Institute | Chattanooga | Tennessee | 37404 | United States |
| SCRI Tennessee Oncology Chattanooga | Chattanooga | Tennessee | 37404 | United States |
| Tennessee Oncology, PLLC | Cleveland | Tennessee | 37311 | United States |
| Tennessee Oncology NASH - SCRI - PPDS | Nashville | Tennessee | 37203 | United States |
| The Sarah Cannon Research Institute. | Nashville | Tennessee | 37203 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| UZ Leuven - Dermatology | Leuven | 3000 | Belgium |
| UZ Leuven - Ophthalmology | Leuven | 3000 | Belgium |
| UZ Leuven | Leuven | 3000 | Belgium |
| The Netherlands Cancer Institute Antoni Van Leeuwenhoek | Amsterdam | North Holland | 1066 CX | Netherlands |
| OLVG locatie Oost | Amsterdam | North Holland | 1091 AC | Netherlands |
| Amsterdam Medical Center (AMC) | Amsterdam | North Holland | 1105 AZ | Netherlands |
| Hospital Universitario Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Universitario Vall d'Hebrón - PPDS | Barcelona | 08035 | Spain |
| Hospital General Universitario Gregorio Marañon | Madrid | 28007 | Spain |
| Clinica Rementeria | Madrid | 28010 | Spain |
| Hospital Universitario 12 Octubre | Madrid | 28041 | Spain |
| Hospital HM Universitario Sanchinarro, CIOCC | Madrid | 28050 | Spain |
| Royal Marsden Hospital - London | London | London, CITY of | SW3 6JJ | United Kingdom |
| Churchill Hospital | Oxford | Oxfordshire | OX3 7LE | United Kingdom |
| Royal Marsden Hospital NHS Foundation Trust | Surrey | Sutton | SM2 5PT | United Kingdom |
| Royal Marsden Hospital NHS Foundation Trust | London | SW3 6JJ | United Kingdom |
| Royal Marsden Hospital -Fulham Road | London | SW36JJ | United Kingdom |
| FG001 | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 milligram per kilogram (mg/kg) IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| FG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| FG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| COMPLETED |
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| NOT COMPLETED |
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| Randomized Phase 2 Period |
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Full Analysis Set (FAS) included all participants who received at least 1 dose of any study drug in Phase 1b and all participants randomized to study treatment in Phase 2.
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1b: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| BG001 | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| BG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| BG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT) | DLT:Adverse event(AE)/abnormal laboratory assessed unrelated-disease,disease progression,intercurrent illness/concomitant medication/therapies resulting inability tolerate 75% dose intensity in Cycle 1.Total bilirubin(TBL)grade(G)>=3 (>3.0*upper limit of normal[ULN)]);AST/ALT>5-8*ULN>5 days,>8*ULN,>3*ULN concurrent TBL>2*ULN;G>=3 serum creatinine,CK elevation,ECG QTcF prolonged,G3 troponin,electrolyte>72 hours,G3/4 amylase/lipase.G4 ANC,platelet count>7 days;G3/4 platelet count,other AE except lymphopenia.G>=3 retinopathy,other disorder>21 days;G2 uveitis/eye pain/blurred vision/decreased visual acuity;G4 other disorder.Decrease LVEF>10% G>=3 cardiac disorders.G3/4 hypertension.G3 fatigue>=7 days,hypersensitivity,infusion reaction,fever>=72 hours/hemodynamic compromise,endocrinopathy.G>=2 interstitial lung disease/pneumonitis;G3 bronchospasm.G3/4 rash,hand foot skin reaction,photosensitivity.G3 colitis;G3/4 diarrhea,nausea/vomiting.Neurologic G3.Other hematologic/nonhematolic G>=3 AE. | Dose-Determining Set (DDS) included all participants in Phase 1b who experienced a DLT or receive at least 75% of the planned binimetinib dose intensity during Cycle 1. | Posted | Count of Participants | Participants | Cycle 1: Day 1 up to Day 28 |
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| Primary | Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | ORR was defined as the percentage of participants who achieved a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<)10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was considered progression. | All participants randomized to study treatment in Phase 2. | Posted | Number | 95% Confidence Interval | Percentage of participants | From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 2: maximum up to 26 months approximately) |
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| Secondary | Phase 1b: Objective Response Rate (ORR) Per RECIST v1.1 | ORR was defined as the percentage of participants who achieved a BOR of CR or PR as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. | All participants who received at least 1 dose of any study treatment in Phase 1b. | Posted | Number | 95% Confidence Interval | Percentage of participants | From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately) |
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| Secondary | Duration of Response (DOR) as Per RECIST v1.1 | DOR was defined as the time between the date of the first documented confirmed response (PR or CR) and the date of the first documented progression or death due to any cause. As per RECIST v1.1: CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures <10 mm. PR was defined as at least 30% decrease in sum of measures (tumor lesions- longest diameter and nodes- short axis) of target lesions, taking as reference baseline sum of diameters. PD was defined as at least 20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. | FAS included all participants who received at least 1 dose of any study drug in Phase 1b and all participants randomized to study treatment in Phase 2. Here, "Overall Number of Participants Analyzed" signifies number of participants who achieved an objective response. There were no participants who had event in Phase 1b and Nivolumab and Binimetinib group of Phase 2. | Posted | Median | 95% Confidence Interval | Months | From date of first documented CR/PR to date of first documented PD, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately, Phase 2: maximum up to 26 months approximately) |
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Complete Response as Per RECIST v1.1 | Complete response as per RECIST v1.1 was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. | FAS included all participants who received at least 1 dose of any study drug in Phase 1b and all participants randomized to study treatment in Phase 2. | Posted | Number | Percentage of participants | From start of the treatment until disease progression, death or initiation of new anticancer therapy, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately) |
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAE) Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 | AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE: AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs: events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy minus 1 day, whichever occurred first. TEAE graded by CTCAE grade 4.03: Grade 3: severe/medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care activities of daily living (ADL); Grade 4: life-threatening consequence, urgent intervention indicated. In this outcome measure, number of participants with 'all grades' and 'Grade 3/4' were reported. | The safety set included of all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately) |
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03: Hematology and Coagulation | Hematological parameters included: Hemoglobin graded high, Hemoglobin graded low, Platelets count graded low, White Blood Cell (WBC) graded high, WBC graded low, Neutrophils graded low, Lymphocytes graded high, Lymphocytes graded low. Coagulation parameters included: International Normalized Ratio (INR) graded high, Activated Partial Thromboplastin Time (aPTT) graded high. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported. | Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Hematology and Coagulation | Hematology parameters: Basophils, Eosinophils, Hematocrit, Monocytes, Red blood cells (RBC). Coagulation parameters: Prothrombin Time. Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Laboratory parameters were graded based on laboratory normal ranges as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported. | Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
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| Secondary | Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on CTCAE v4.03: Chemistry | Abnormalities: Albumin graded low, Alkaline phosphatase (ALP) graded high, Alanine aminotransferase (ALT) graded high, Aspartate aminotransferase (AST) graded high, Bilirubin graded high, Amylase graded high, Creatinine graded high, Corrected calcium graded high, Creatine Kinase (CK) graded high, Glucose graded high, Glucose graded low, Lipase graded high, Magnesium graded high, Magnesium graded low, Potassium graded high, Potassium graded low, Sodium graded high and Sodium graded low. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening. A grade 0 was assigned for all non-missing values not graded as 1 or higher. If value was graded >=1 but falls within the normal range, the grade was reset to 0. Categories with at least 1 non-zero data values are reported. | Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
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| Secondary | Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on Normal Range: Chemistry and Thyroid Function | Chemistry laboratory parameters: Blood urea nitrogen (BUN), Total protein, Chloride, Cancer antigen 19-9 (CA 19-9), Brain natriuretic peptide (BNP), Bicarbonate, Direct bilirubin, Carcinoembryonic antigen (CEA), Lactate dehydrogenase (LDH), Uric acid, Troponin I. Thyroid panel laboratory parameters: Thyroid-stimulating hormone (TSH), Free triiodothyronine (T3), Free thyroxine (T4). Laboratory values were as per laboratory normal ranges. Values above range were reported as high and values below range as low. Shift in chemistry and thyroid panel severity from baseline grade low, normal, high and missing to the post baseline grades as low, normal, high and missing are reported in this outcome measure. Categories with at least 1 non-zero data values are reported. | Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Abnormal Hepatic Laboratory Values | Criteria for abnormal hepatic laboratory parameters: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT): >3* upper limit of normal (ULN), >5*ULN, >8*ULN, >10*ULN, >20*ULN; Total bilirubin (TBL) >1.5*ULN, >2*ULN; Alkaline phosphatase (ALP) >2*ULN, >3*ULN. Categories with at least 1 non-zero data values are reported. | Safety set included of all participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | Phase 1b: Baseline up to 30 days after last dose (maximum up to 9 months approximately), Phase 2: Baseline up to 30 days after last dose (maximum up to 26 months approximately) |
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| Secondary | Concentration Versus Time Summary of Plasma Concentration of Binimetinib | The pharmacokinetic analysis set included of all participants who received at least 1 dose of binimetinib and have at least one evaluable bioanalytical result. Here "Number Analyzed" signifies number of participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter | 1.5 hours post dose of binimetinib on Day 1, 15 of Cycle 1; pre dose of binimetinib on Day 15 of Cycle 1, 2, 3, 4, 5 |
|
All-Cause Mortality: From start of the treatment up to 150 days after last dose (Phase 1b: maximum up to 13 months approximately and Phase 2: maximum up to 30 months approximately); TEAEs (including serious and other AEs): From start of the treatment up to 30 days after last dose (Phase 1b: maximum up to 9 months approximately and Phase 2: maximum up to 26 months approximately)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety set was evaluated. Both TEAE and treatment related AEs were monitored.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1b: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | 8 | 10 | 5 | 10 | 10 | 10 |
| EG001 | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. | 8 | 11 | 6 | 11 | 11 | 11 |
| EG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | 20 | 27 | 12 | 27 | 27 | 27 |
| EG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. | 21 | 27 | 11 | 27 | 27 | 27 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocarditis | Cardiac disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypophysitis | Endocrine disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Abdominal infection | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Empyema | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Infected seroma | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Klebsiella bacteraemia | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Periorbital cellulitis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Myositis | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v21.0 | Non-systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Nephritis | Renal and urinary disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Superior vena cava syndrome | Vascular disorders | MedDRA v21.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Ventricular hypokinesia | Cardiac disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Periorbital oedema | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Eyelid oedema | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Subretinal fluid | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Macular oedema | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Photopsia | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Retinopathy | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dry age-related macular degeneration | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Eye oedema | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Vitreous detachment | Eye disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Glossitis | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Mesenteric arterial occlusion | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Face oedema | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Abdominal injury | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
| |
| Scratch | Injury, poisoning and procedural complications | MedDRA v21.0 | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Troponin T increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Troponin I increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Electrocardiogram abnormal | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Intraocular pressure increased | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Prothrombin time prolonged | Investigations | MedDRA v21.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v21.0 | Non-systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v21.0 | Non-systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pruritus genital | Reproductive system and breast disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Scrotal oedema | Reproductive system and breast disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Dermatitis exfoliative generalised | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Exfoliative rash | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA v21.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA v21.0 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 9, 2020 | Oct 4, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C581313 | binimetinib |
| D000077594 | Nivolumab |
| D000074324 | Ipilimumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Death |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Completed follow-up per protocol |
|
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG001 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
|
|
| OG001 | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
|
|
| OG001 | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| OG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| OG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
|
|
| OG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| OG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
|
|
| OG001 | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| OG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| OG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
|
|
| OG001 | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| OG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| OG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
|
|
| Phase 1b: Nivolumab+Ipilimumab+Binimetinib |
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| OG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| OG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
|
|
| OG001 | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| OG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| OG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
|
|
| OG001 | Phase 1b: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days. |
| OG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| OG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
|
|
Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received binimetinib at a starting dose of 45 mg tablet BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion. Binimetinib dose modification to intermitted dosing (3 weeks on treatment and 1 week off treatment) with 45 mg dose or dose reduction to 30 mg BID or 30 mg intermittent dosing based on investigator's decision as per its tolerability among participants. Participants then followed up for safety for around 150 days.
| OG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| OG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
|
|
| OG002 | Phase 2: Nivolumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle, until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
| OG003 | Phase 2: Nivolumab+Ipilimumab+Binimetinib | Participants with previously treated MSS metastatic colorectal cancer with RAS mutation received 45 mg binimetinib tablet orally BID along with 480 mg IV dose of nivolumab every 4 weeks in each 28 day treatment cycle. Ipilimumab was administered at the dose of 1 mg/kg IV every 8 weeks after completion of nivolumab infusion until disease progression, unacceptable toxicity, withdrawal of informal consent, initiation of subsequent anticancer therapy, lost to follow-up or death. Participants then followed up for safety for around 150 days. |
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