The STARBOARD Study: Phase 3 Study of Encorafenib and Binimetinib Plus Pembrolizumab in BRAF V600E/K Mutation-Positive Metastatic or Unresectable Locally Advanced Melanoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Sep 2021 → ongoing

Decision date (initial)

2024-05-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2024-512038-13-00

EudraCT number

2020-004850-31

ClinicalTrials.gov

NCT04657991

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacoeconomic, Therapy, Pharmacogenomic, Pharmacokinetic

Safety Lead-In:
To determine the RP3D of encorafenib and binimetinib when given in combination with pembrolizumab.
Randomized Phase 3:
To compare the efficacy of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus placebo plus pembrolizumab (Control Arm) with respect to OR by BICR assessment.

Secondary objectives 4

1. Safety Lead-In: To assess the overall safety and tolerability of encorafenib and binimetinib plus pembrolizumab.
2. Safety Lead In: To assess the efficacy of encorafenib and binimetinib plus pembrolizumab.
3. Safety Lead In: To characterize the PK of encorafenib and binimetinib when administered in combination with pembrolizumab.
4. Randomized Phase 3: To compare the efficacy of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus placebo plus pembrolizumab (Control Arm) with respect to PFS by BICR assessment

Conditions and MedDRA coding

Metastatic or unresectable locally advanced BRAF V600E/K mutation positive melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Male or female participants ≥18 years of age at the time of informed consent.
2. 2. Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition.
3. 3. Documented evidence of a BRAF V600E or V600K mutation
4. 4. Submission of adequate tumor tissue for central laboratory testing of BRAF V600E/K mutation is required for all participants during the screening period and prior to enrollment (SLI)/randomization (Phase 3).
5. 5. SLI Participants: Have not received more than 1 prior systemic therapy for metastatic or locally advanced melanoma.
6. 6. Phase 3 Participants: Have not received prior first-line systemic therapy for metastatic or unresectable locally advanced melanoma.
7. 7. Have at least 1 measurable lesion per RECIST v1.1.
8. 8. ECOG PS of 0 or 1, and adequate organ and cardiac function, including LVEF ≥50% by cardiac imaging.

Exclusion criteria 10

1. 1. Mucosal or ocular melanoma
2. 2. Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment in the past 2 years.
3. 3. Clinically significant cardiovascular disease.
4. 4. History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to enrollment (SLI)/randomization (Phase 3).
5. 5. History or current evidence of RVO or current risk factors for RVO.
6. 6. Concurrent neuromuscular disorder that is associated with the potential of elevated CK.
7. 7. Any active infection requiring systemic therapeutic treatment within 2 weeks prior to enrollment (SLI)/ randomization (Phase 3).
8. 8. Current noninfectious pneumonitis/interstitial lung disease or history of noninfectious pneumonitis/interstitial lung disease requiring steroids, or history of radiation pneumonitis.
9. 9. Prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases.
10. 10. Previous administration with an investigational drug ≤ 6 months prior to enrollment (SLI)/randomization (Phase 3)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety Lead-In: Incidence of DLTs.
2. Randominzed Phase 3: OR, defined as confirmed BOR of either CR or PR, as determined by BICR assessment per RECIST v1.1 from randomization to the earliest of PD, start of subsequent anticancer therapy, or death due to any cause

Secondary endpoints 4

1. 1. Safety Lead-In: Incidence and severity of AEs graded according to the NCI CTCAE v4.03* and changes in clinical laboratory parameters, vital signs, and cardiac assessments.
2. 2. Safety Lead-In: OR, PFS, DC, TTR
3. 3. Safety Lead-In: Plasma concentration-time profiles and PK parameter estimates for encorafenib and binimetinib.
4. 4. Randomized Phase 3: PFS, defined as the time from the date of randomization to the date of first documented disease progression, as determined by BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 14

Locations

11 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 123 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

30 submissions — initial application plus substantial / non-substantial modifications