Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation. (COLUMBUS-AD)

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Pierre Fabre

Status and phase

Active, not recruiting
Phase 3

Conditions

Melanoma

Treatments

Drug: Placebo to match Encorafenib ; Placebo to match Binimetinib
Drug: Encorafenib and Binimetinib

Study type

Interventional

Funder types

NETWORK
Industry

Identifiers

NCT05270044
W00090GE303/EORTC-2139-MG

Details and patient eligibility

About

The purpose of the Columbus-AD study is to evaluate the efficacy and safety of 12 months of encorafenib in combination with binimetinib in adjuvant setting of BRAF V600E/K mutant stage IIB/C melanoma versus the current standard of care (surveillance).

Full description

This is a randomized triple-blind placebo-controlled international multicenter phase III superiority clinical trial. Participants with completely resected cutaneous melanoma and documented BRAF V600E/K status by central assay will be randomized 1 to 1 to receive either treatment with encorafenib and binimetinib or their two placebos for 12 months. Patients will be stratified according to the stage of the disease according to AJCC version 8 between: stage IIB (i.e., pT3b or pT4a) stage IIC (i.e., pT4b). The long-term evaluation of all endpoints (including information about the occurrence of new treatment-related adverse events, if any) will take place 10 years from the randomization of the last patient.

Enrollment

815 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Pre-Screening * Male or female ≥ 18 years of age; * Surgically resected, with tumour free margins, and histologically/pathologically confirmed new diagnosis of stage II (pT3b-pT4bN0) cutaneous melanomaa; * Sentinel node (SN) biopsy within 14 weeks from initial diagnosis of melanoma. * Sentinel node (SN) staged node negative (pN0); * Available tumour sample for central determination of the BRAF V600E/K mutation. Screening * Melanoma confirmed centrally to be BRAF V600E/K mutation-positive; * Participant still free of disease as evidenced by the required baseline imaging and physical/dermatological assessments performed respectively within 6 weeks and 2 weeks before randomization (Day 1); * No more than 12 weeks elapsed between full surgical resection (including SLNB) and randomization; * Recovered from definitive surgery (e.g., complete wound healing, no uncontrolled wound infections or indwelling drains); * ECOG performance status of 0 or 1; * Adequate haematological function as defined as Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L and Hemoglobin ≥ 9.0 g/dL; * Adequate renal function as defined as Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min; * Adequate electrolytes, defined as serum potassium and magnesium levels within institutional normal limits; * Adequate hepatic function as defined as Serum total bilirubin ≤ 1.5 x ULN and \< 2 mg/dL, Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 x ULN; * Adequate cardiac function as defined as LVEF ≥ 50% as determined by MUGA scan or echocardiogram and Mean triplicate QTcF value ≤ 480 msec and no history of QT syndrome; * Adequate coagulation function, defined as INR ≤1.5× ULN unless the patient is receiving anticoagulant therapy as long as PT or aPTT is within the therapeutic range; * Negative serum β-HCG test (female patient of childbearing potential only) performed within 3 days prior to Day 1; * Female patients of child-bearing potential and male patients must agree to follow the protocol's contraception guidance during the treatment period and for ≥30 days after last administration.

Exclusion criteria

Pre-screening * Unknown ulceration status; * Uveal and mucosal melanoma; * Clinically apparent metastases (N+/M1); * Microsatellites, satellites and/or in-transit metastases, * Local (scar) recurrences. Screening * Breast feeding women; * Pregnant women; * History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO; * History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to randomization; * History of previous or concurrent malignancy within preceding 3 years or any condition with a life expectancy of less than 5 years; * Participants with a prior cancer associated with RAS mutation; * Prior systemic anticancer therapy for melanoma or radiotherapy for melanoma; * Hypersensitivity to the study drugs or to any of the excipients; * Participants with severe lactose intolerance (e.g., Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption); * Impaired cardiovascular function or clinically significant cardiovascular diseases; * Neuromuscular disorders that are associated with CK \> ULN (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy); * Non-infectious pneumonitis and Interstitial Lung Disease; * Positive SARs-CoV-2 or variants of SARs-CoV2 RT-PCR test at screening or suspected to be infected with SARs-CoV2 or variants of SARsCoV2 with confirmation pending; * Active bacterial, fungal, or viral infection, including, but not limited to HBV, HCV, and known HIV or AIDS-related illness, or an infection requiring systemic therapeutic treatment within 2 weeks prior to randomization.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

815 participants in 2 patient groups, including a placebo group

Arm A
Experimental group
Description:
Encorafenib and Binimetinib
Treatment:
Drug: Encorafenib and Binimetinib
Arm B
Placebo Comparator group
Description:
Placebo to match Encorafenib Placebo to match Binimetinib
Treatment:
Drug: Placebo to match Encorafenib ; Placebo to match Binimetinib

Trial contacts and locations

155

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Central trial contact

Isabelle Klauck, MD

Data sourced from clinicaltrials.gov

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