Phase 2 Study of Encorafenib and Binimetinib Plus Pembrolizumab in Participants With BRAF V600E/K Mutation-Positive Melanoma Who Progressed During or After Prior Treatment with Anti-PD-1 Therapy

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 - Portside

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-003640-24-SK

Enrollment

150

Registered

2022-11-11

Start date

2023-01-16

Completion date

Unknown

Last updated

2024-06-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

metastatic or unresectable locally advanced BRAF V600E/K mutation-positive melanoma MedDRA version: 20.0 Level: LLT Classification code 10040891 Term: Skin melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLT Classification code 10027156 Term: Skin melanomas (excl ocular) System Organ Class: 100000004858 MedDRA version: 21.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Org

Interventions

Trade Name: BRAFTOVI® Product Name: Encorafenib Product Code: PF-07263896 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Encorafenib CAS Number: 1269440-17-6 Current Sponsor code: PF-0726389

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Participants must meet the following key inclusion criteria to be eligible for enrollment into the study: - 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 for central laboratory testing of BRAF V600E/K mutation and biomarkers is required for all participants during the screening period and prior to randomization. - 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 1 measurable lesion per RECIST v1.1. - ECOG PS of 0-1, and adequate organ and cardiac function, including LVEF =50% by cardiac imaging. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40

Exclusion criteria

Exclusion criteria: Participants with any of the following key characteristics/conditions will be excluded: - 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 noninfectious pneumonitis/ILD or history of noninfectious pneumonitis/ILD 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 anticancer agent for the adjuvant or first-line treatment of melanoma prior to randomization. - Previous participation in the Pfizer C4221016 STARBOARD Study.

Design outcomes

Primary

Measure	Time frame
Main Objective: To compare the efficacy of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus nivolumab and ipilimumab (Control Arm) with respect to ORR.;Secondary Objective: - To compare the efficacy of the Triplet Arm versus the Control Arm with respect to PFS. - To compare the efficacy of the Triplet Arm versus the Control Arm with respect to OS.;Primary end point(s): ORR, defined as the proportion of participants with a confirmed best overall response of either CR or PR, as determined by investigator assessment per RECIST v1.1 from randomization to the earliest of PD, start of subsequent anticancer therapy, or death due to any cause.;Timepoint(s) of evaluation of this end point: Throughout the duration of the study; the analysis of ORR and PFS will be both performed at the time on the achievement of the required number of PFS events (88) to run the PFS analysis: assuming non-uniform enrollment over 14 months, 88 PFS events are anticipated to occur approximately 21 months after the first participant is randomized	—

Measure

Time frame

Main Objective: To compare the efficacy of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus nivolumab and ipilimumab (Control Arm) with respect to ORR.;Secondary Objective: - To compare the efficacy of the Triplet Arm versus the Control Arm with respect to PFS. - To compare the efficacy of the Triplet Arm versus the Control Arm with respect to OS.;Primary end point(s): ORR, defined as the proportion of participants with a confirmed best overall response of either CR or PR, as determined by investigator assessment per RECIST v1.1 from randomization to the earliest of PD, start of subsequent anticancer therapy, or death due to any cause.;Timepoint(s) of evaluation of this end point: Throughout the duration of the study; the analysis of ORR and PFS will be both performed at the time on the achievement of the required number of PFS events (88) to run the PFS analysis: assuming non-uniform enrollment over 14 months, 88 PFS events are anticipated to occur approximately 21 months after the first participant is randomized

—

Secondary

Measure	Time frame
Secondary end point(s): 1. PFS, defined as the interval of time between 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. 2. OS, defined as the time from date of randomization to the date of death due to any cause or the last known alive date. 3. DOR, defined as the 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. 4. DCR, defined as the proportion of participants with a confirmed best overall response of CR, PR or SD, as determined by investigator assessment per RECIST v1.1. 5. TTR, defined as the 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. 6. PFS2, defined as the time from the date of randomization to the date of discontinuation of next-line treatment after first objective disease progression by investigator assessment per RECIST v1.1, second objective disease progression after initiation of next-line treatment, as determined by investigator assessment, or death due to any cause, whichever occurs first. 7. Incidence and severity of AEs, and changes in clinical laboratory parameters, vital signs, and cardiac assessments. 8. EORTC QLQ-C30: change from baseline in the global health status/QoL score and all other subscales scores. 9. EQ-5D-5L: change from baseline in the index score and VAS. 10. BRAF V600E/K VAF and/or overall mean VAF from ctDNA analysis of plasma samples collected at baseline and on treatment.;Timepoint(s) of evaluation of this end point: throughout the study	—

Measure

Time frame

Secondary end point(s): 1. PFS, defined as the interval of time between 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. 2. OS, defined as the time from date of randomization to the date of death due to any cause or the last known alive date. 3. DOR, defined as the 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. 4. DCR, defined as the proportion of participants with a confirmed best overall response of CR, PR or SD, as determined by investigator assessment per RECIST v1.1. 5. TTR, defined as the 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. 6. PFS2, defined as the time from the date of randomization to the date of discontinuation of next-line treatment after first objective disease progression by investigator assessment per RECIST v1.1, second objective disease progression after initiation of next-line treatment, as determined by investigator assessment, or death due to any cause, whichever occurs first. 7. Incidence and severity of AEs, and changes in clinical laboratory parameters, vital signs, and cardiac assessments. 8. EORTC QLQ-C30: change from baseline in the global health status/QoL score and all other subscales scores. 9. EQ-5D-5L: change from baseline in the index score and VAS. 10. BRAF V600E/K VAF and/or overall mean VAF from ctDNA analysis of plasma samples collected at baseline and on treatment.;Timepoint(s) of evaluation of this end point: throughout the study

—

Countries

Canada, Czechia, Germany, Israel, Italy, Poland, Slovakia, Spain, Switzerland, United Kingdom, United States

Contacts

Public ContactClinical Trials.gov Call Centre

Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com+1800 7181021

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026