KEY TAKEAWAYS
- The phase 3 STARBOARD trial will assess the effectiveness and safety of enco + bini + pembro versus placebo + pembro for patients with unresectable locally advanced or metastatic BRAF V600-mutant melanoma.
- The trial design incorporated a safety lead-in phase to establish the RP3D and began enrolling patients in June 2022.
BRAF V600 mutations are frequently detected in metastatic melanoma, where they constantly activate the MAPK pathway, driving the progression of melanoma. Typically, patients (pts) with BRAF V600-mutant metastatic melanoma are treated with a combination of BRAF inhibitors (BRAFi) like enco and MEK inhibitors (MEKi), or immune checkpoint inhibitors (CPIs) such as pembro. However, these treatments have their limitations. BRAFi and MEKi may enhance the responsiveness of BRAF V600-mutant tumors to CPIs. Previous studies have reported improved progression-free survival (PFS) in advanced BRAF V600-mutant melanoma pts who received a combination of BRAFi, MEKi, and CPIs compared to those who received targeted therapy alone.
This phase 3 trial aimed to assess the effectiveness and safety of enco + bini + pembro versus placebo + pembro for patients with unresectable locally advanced or metastatic BRAF V600-mutant melanoma. A safety lead-in (SLI) phase was incorporated to determine the recommended phase 3 dose (RP3D) before initiating phase 3 of the trial.
The STARBOARD trial is a randomized, double-blind, placebo-controlled, phase 3 study involving approximately 600 pts with advanced melanoma harboring BRAF V600 mutations. Patients will be grouped based on their prior systemic adjuvant treatment (CPI, BRAFi/MEKi, or none) and disease stage according to AJCC 8th edition criteria (IIIB, IIIC, IIID, IV M1a[0], and IV M1b[0] vs IV M1a[1], IV M1b[1], IV M1c[0], IV M1c[1], IV M1d[0], and IV M1d[1]). Eligible pts must have measurable disease (according to RECIST 1.1), an ECOG performance status of 0 or 1, and satisfactory bone marrow, hepatic, and renal function. They must not have received prior systemic therapy for unresectable or metastatic melanoma, although adjuvant treatment with BRAFi/MEKi, anti-PD-1, or anti-CTLA-4 is allowed. Patients with symptomatic brain metastases are not included in the study. RP3D was established in May 2022, and phase 3 enrollment commenced in June 2022.
Source: https://eado2023.com/wp-content/uploads/2023/04/Abstract-Band_EADO2023_Stand-21-04-2023-kl.pdf
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04657991
Schadendorf, D., Dummer, R., Robert, C., Ribas, A., Sullivan, R., Panella, T., McKean, M., Santos, E., Clancy, J., Polli, A., di Pietro, A., Ascierto, P. Randomized phase 3 study (STARBOARD) evaluating encorafenib (enco) + binimetinib (bini) + pembrolizumab (pembro) for first-line treatment of unresectable locally advanced or metastatic BRAF V600-mutant melanoma.
