MSSPhase 2NCT03271047
Study of Binimetinib + Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation
A Phase 2 study testing binimetinib, nivolumab and ipilimumab in people with MSS and RAS-mutant Colorectal Cancer, run by Pfizer at 50 sites in 5 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MSS, RAS-mutant Colorectal Cancer
- What is being tested?
- binimetinib, nivolumab and ipilimumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 50 sitesin 5 countries
- Study dates
- 18 Oct 2017to 25 Feb 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- If a fresh tissue sample is provided, a blood sample is required.
- 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:
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- were unable to tolerate the prior first-line regimen
- experienced disease progression during or after prior first-line regimen for metastatic disease
- progressed during or within 3 months of completing adjuvant chemotherapy. Note: Generally, treatments that are separated by an event of progression are considered different regimens.
- 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
Who cannot join
- Prior treatment with any MEK inhibitor, an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Any untreated central nervous system (CNS) lesion.
- Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Known history of retinal vein occlusion (RVO).
- Known history of Gilbert's syndrome.
- Pregnant or breastfeeding females.
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- Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to first day of study treatment:
- History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli.
- Uncontrolled hypertension defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy.
- Concurrent neuromuscular disorder that is associated with the potential of elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
- Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus.
Trial locations and contacts
50 sites in 5 countries.
50 sites in 5 countries
United States33 sites
Sarah Cannon Research Institute
Chattanooga, Tennessee, 37404
SCRI Tennessee Oncology Chattanooga
Chattanooga, Tennessee, 37404
Siteman Cancer Center - Barnes St. Peters
City of Saint Peters, Missouri, 63376
Tennessee Oncology, PLLC
Cleveland, Tennessee, 37311
Siteman Cancer Center - West County
Creve Coeur, Missouri, 63141
Siteman Cancer Center - North County
Florissant, Missouri, 63031
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana CTSI Clinical Research Center (ICRC)
Indianapolis, Indiana, 46202
Indiana University Health Hospital
Indianapolis, Indiana, 46202
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Investigational Drug Services IUHSCC
Indianapolis, Indiana, 46202
Sidney &Lois Eskenazi Hospital
Indianapolis, Indiana, 46202
Spring Mill Medical Center
Indianapolis, Indiana, 46290
UCLA Hematology/Oncology
Los Angeles, California, 90095
Tennessee Oncology NASH - SCRI - PPDS
Nashville, Tennessee, 37203
The Sarah Cannon Research Institute.
Nashville, Tennessee, 37203
Christiana Care Health Services, Helen F. Graham Cancer Center Pharmacy, Suite 3200
Newark, Delaware, 19713
Christiana Care Health Services, Helen F. Graham Cancer Center
Newark, Delaware, 19713
Christiana Care Oncology Hematology, Helen F Graham Cancer Center, Suite 2400
Newark, Delaware, 19713
Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center
Newark, Delaware, 19713
Christiana Care Health Services, Christiana Hospital
Newark, Delaware, 19718
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Investigational Drug Service of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Hematology Oncology Associates of the Treasure Coast
Port Saint Lucie, Florida, 34952
UCLA Hematology/Oncology - Santa Monica
Santa Monica, California, 90404
Center for Outpatient Health (Dermatology Clinic)
St Louis, Missouri, 63108
Center for Outpatient Health (Ophthalmology Clinic)
St Louis, Missouri, 63108
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center - South County
St Louis, Missouri, 63129
Georgetown University Medical Center Department of Pharmacy, Research
Washington D.C., District of Columbia, 20007
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Spain6 sites
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Universitario Vall d'Hebrón - PPDS
Barcelona, 08035
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Clinica Rementeria
Madrid, 28010
Hospital Universitario 12 Octubre
Madrid, 28041
Hospital HM Universitario Sanchinarro, CIOCC
Madrid, 28050
United Kingdom5 sites
Royal Marsden Hospital - London
London, London, CITY of, SW3 6JJ
Royal Marsden Hospital NHS Foundation Trust
London, SW3 6JJ
Royal Marsden Hospital -Fulham Road
London, SW36JJ
Churchill Hospital
Oxford, Oxfordshire, OX3 7LE
Royal Marsden Hospital NHS Foundation Trust
Surrey, Sutton, SM2 5PT
Belgium3 sites
UZ Leuven - Dermatology
Leuven, 3000
UZ Leuven - Ophthalmology
Leuven, 3000
UZ Leuven
Leuven, 3000
Netherlands3 sites
The Netherlands Cancer Institute Antoni Van Leeuwenhoek
Amsterdam, North Holland, 1066 CX
OLVG locatie Oost
Amsterdam, North Holland, 1091 AC
Amsterdam Medical Center (AMC)
Amsterdam, North Holland, 1105 AZ
About this study
Official title: An Open-label Phase 1b/2 Study of Binimetinib Administered in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation
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.
- Conditions
- MSS, RAS-mutant Colorectal Cancer
- Being tested
- binimetinib, nivolumab, ipilimumab
- Keywords
- cancer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
binimetinibDrug
Orally, twice daily.
nivolumabDrug
Intravenously (IV) every 4 weeks (Q4W)
ipilimumabDrug
intravenously (IV) every 8 weeks (Q8W)
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b / Arm 1A | Experimental | binimetinib + nivolumab Receives: Drug: binimetinib; Drug: nivolumab |
| Phase 1b / Arm 1B | Experimental | binimetinib + nivolumab + ipilimumab Receives: Drug: binimetinib; Drug: nivolumab; Drug: ipilimumab |
| Phase 2 / Arm 2A | Experimental | binimetinib + nivolumab Receives: Drug: binimetinib; Drug: nivolumab |
| Phase 2 / Arm 2B | Experimental | binimetinib + nivolumab + ipilimumab Receives: Drug: binimetinib; Drug: nivolumab; Drug: ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2017
- Study start18 Oct 2017
- Primary completion13 Oct 2020
- Study completion25 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MSSStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- In phase 1 it is sequential and then in phase 2 it is parallel.
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03271047
- Sponsor's protocol ID
- ARRAY-162-202
- Other IDs
- C4211004, 2017-003464-12, 2017
- Status last verified
- Dec 2021
- First submitted
- 31 Aug 2017
- Last updated
- 4 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 38600471
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase 1b/2 Study of Binimetinib Administered in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation
- ClinicalTrials.gov ID
- NCT03271047
- Acronym / sponsor ID
- ARRAY-162-202
- Conditions
- MSS, RAS-mutant Colorectal Cancer
- Keywords
- cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 18 Oct 2017 (actual)
- Primary completion
- 13 Oct 2020 (actual)
- Study completion
- 25 Feb 2021 (actual)
- First posted
- 1 Sep 2017 (actual)
- Results
- Posted 2 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- In phase 1 it is sequential and then in phase 2 it is parallel.
| Arm | Type | Receives |
|---|---|---|
| Phase 1b / Arm 1A | Experimental | Drug: binimetinib, Drug: nivolumabbinimetinib + nivolumab |
| Phase 1b / Arm 1B | Experimental | Drug: binimetinib, Drug: nivolumab, Drug: ipilimumabbinimetinib + nivolumab + ipilimumab |
| Phase 2 / Arm 2A | Experimental | Drug: binimetinib, Drug: nivolumabbinimetinib + nivolumab |
| Phase 2 / Arm 2B | Experimental | Drug: binimetinib, Drug: nivolumab, Drug: ipilimumabbinimetinib + nivolumab + ipilimumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
Key exclusion criteria (13 listed)
- Prior treatment with any MEK inhibitor, an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Any untreated central nervous system (CNS) lesion.
- Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Known history of retinal vein occlusion (RVO).
- Known history of Gilbert's syndrome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| binimetinibOrally, twice daily. | Drug | Phase 1b / Arm 1A, Phase 1b / Arm 1B, Phase 2 / Arm 2A, Phase 2 / Arm 2B |
| nivolumabIntravenously (IV) every 4 weeks (Q4W) | Drug | Phase 1b / Arm 1A, Phase 1b / Arm 1B, Phase 2 / Arm 2A, Phase 2 / Arm 2B |
| ipilimumabintravenously (IV) every 8 weeks (Q8W) | Drug | Phase 1b / Arm 1B, Phase 2 / Arm 2B |
Primary outcome
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT)
Time frame: Cycle 1: Day 1 up to Day 28
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.
Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Time frame: 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)
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.
10 secondary outcomes
Phase 1b: Objective Response Rate (ORR) Per RECIST v1.1
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38600471Elez 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
50 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing binimetinib, nivolumab and ipilimumab in people with MSS and RAS-mutant Colorectal Cancer, run by Pfizer at 50 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, Spain, United Kingdom, Belgium, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLT) (time frame: Cycle 1: Day 1 up to Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03271047, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2022.