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Clinical Trial Details

Geo Regions

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Melanoma

Encorafenib

Binimetinib

A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF ENCORAFENIB AND BINIMETINIB PLUS PEMBROLIZUMAB VERSUS NIVOLUMAB AND IPILIMUMAB IN PARTICIPANTS WITH BRAF V600E/K MUTATION-POSITIVE MELANOMA WHO PROGRESSED DURING OR AFTER PRIOR TREATMENT WITH ANTI-PD-1 THERAPY
Phase 2
NCT05926960

Active enrolling

Globe
Locations

Czechia, Germany, Italy, Poland, Slovakia, Spain, United Kingdom

Study design

Participant Group/Arm

EXPERIMENTAL: Triplet

encorafenib and binimetinib in combination with pembrolizumab

Intervention/Treatment

DRUG: encorafenib

encorafenib

DRUG: binimetinib

binimetinib

DRUG: pembrolizumab

pembrolizumab

Participant Group/Arm

ACTIVE_COMPARATOR: Doublet

ipilimumab and nivolumab

Intervention/Treatment

DRUG: ipilimumab

ipilimumab

DRUG: nivolumab

nivolumab

Key eligibility criteria

Inclusion criteria
  • Male or female participants ≥18 years of age at the time of informed consent.
  • Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition.
  • Documented evidence of a BRAF V600E or V600K mutation.
  • Availability of adequate tumor tissue (archival or newly obtained; block or slides) to submit to the sponsor central laboratory(ies) during the screening period for central biomarker analyses .
  • Must have received only 1 prior line of systemic therapy for melanoma (either adjuvant therapy or first-line anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab)
  • Must have anti-PD-1 resistant disease (primary or secondary) with confirmed disease progression per RECIST v1.1 either during or after receipt of an approved anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab) for melanoma, defined according to the SITC Immunotherapy Resistance Taskforce (Kluger et al, 2020).
  • Have at least one measurable lesion per RECIST v1.1.
  • ECOG PS of 0-1, and adequate organ and cardiac function, including LVEF ≥50% by cardiac imaging.
Exclusion criteria
  • Mucosal or ocular melanoma.
  • Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment with chronic systemic steroid therapy or any other form of immunosuppressive therapy within the past 2 years.
  • Clinically significant cardiovascular diseases.
  • History of thromboembolic or cerebrovascular events ≤12 weeks prior to randomization.
  • History or current evidence of RVO or current risk factors for RVO.
  • Concurrent neuromuscular disorder that is associated with the potential of elevated CK.
  • Active bacterial, fungal, or viral infection requiring systemic therapeutic treatment within 2 weeks prior to randomization.
  • Current non-infectious pneumonitis/interstitial lung disease or history of noninfectious pneumonitis/interstitial lung disease requiring steroids.
  • Prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases.
  • Participants who permanently discontinued prior anti-PD-1 therapy due to toxicity or will be unable to tolerate combination therapy based on investigator judgement are excluded.
  • Prior treatment with ipilimumab; prior combined immunotherapy blockade with anti-PD-1/L-1; prior treatment with a BRAFi and/or MEKi; or previous administration of an investigational anti-cancer agent for the adjuvant or first-line treatment of melanoma prior to randomization.

Key dates

Study start date
  • June 2023
Estimated primary completion date
  • May 2027

Key endpoints

Primary Outcome Measures
Outcome Measure

Objective Response Rate (ORR) is defined as the proportion of participants in each treatment arm with a confirmed best overall response of either Complete Response (CR) or Partial Response (PR), as determined by investigator assessment per RECIST v1.1

Time Frame

Time from the date of randomization to the earliest date disease progression, or start of subsequent anticancer therapy, or death due to any cause (assessed up to approximately 48 months).

Secondary Outcome Measures:
Outcome Measure

Progression Free Survival in each treatment arm

Time Frame

Time from the date of randomization to the earliest date of disease progression, as determined by investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first (assessed up to approximately 48 months)

Outcome Measure

Overall Survival in each treatment arm

Time Frame

Time from date of randomization to the date of death due to any cause or the last known alive date (assessed up to approximately 48 months)

Outcome Measure

Duration of Response (CR or PR) in each treatment arm

Time Frame

Time from the date of the first documented response (CR or PR) to the earliest date of disease progression, as determined by investigator assessment per RECIST v1.1, or death due to any cause (assessed up to approximately 48 months)

Outcome Measure

Disease Control Rate (proportion of participants with a confirmed best overall response of CR, PR or SD) in each treatment arm

Time Frame

Time from the date of randomization to the earliest date of disease progression, or start of subsequent anticancer therapy (assessed up to approximately 48 months)

Outcome Measure

Time to Response (CR or PR)

Time Frame

Time from the date of randomization to the date of first documented response (CR or PR), as determined by investigator assessment per RECIST v1.1 (assessed up to approximately 48 months)

Outcome Measure

Progression Free Survival 2 in each treatment arm

Time Frame

Time from date of randomization to date of discontinuation of next-line treatment after 1st disease progression, 2nd disease progression after initiation of next line treatment, or death due to any cause (assessed up to approximately 48 months)

Outcome Measure

Incidence and severity of Adverse Events (AEs) and changes in clinical laboratory parameters, vital signs, and cardiac assessments.

Measure Description

Number of participants with treatment emergent Adverse Events as as assessed per National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], version 4.03).

Time Frame

Time from first dose of study intervention through 28 days after the last dose of study intervention

Outcome Measure

Patient Reported Outcomes using EORTC QLQ-C30 questionnaires in each treatment arm

Measure Description

EORTC (European Organization for Research and Treatment of Cancer) QLQ-30 includes 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/Quality of Life scale

Time Frame

Change from Baseline until Progressive Disease, death, withdrawal of consent, lost to follow-up, or end of study, whichever occurs first (assessed up to approximately 48 months)

Outcome Measure

Patient Reported Outcomes using EuroQOL EQ-5D-5L questionnaires in each treatment arm

Measure Description

The EQ-5D-5L is a standardized measure of health utility that provides a single index value of health status and contains 1 item for each of 5 dimensions of HRQoL (ie, mobility, self-care, usual activities, pain or discomfort, and anxiety or depression).

Time Frame

Change from Baseline until Progressive Disease, death, withdrawal of consent, lost to follow-up, or end of study, whichever occurs first (assessed up to approximately 48 months)

Outcome Measure

BRAF V600E/K Variant Allele Frequency and/or overall mean Variant Allele Frequency from circulating tumour DNA analysis in each treatment arm

Time Frame

Change from baseline, Day 1 of Cycle 2 (after 3 weeks), and End of Treatment (assessed up to approximately 48 months)

Number of participants

150

Collaborators and investigators

Sponsor: Pfizer

Collaborator: Merck Sharpe & Dohme LLC

This information is current as of June 3rd 2024.