| Official Title | A Phase 2 Master Protocol to Assess the Efficacy and Safety of FORE8394, an Inhibitor of BRAF Class 1 and Class 2 Alterations, in Participants With Cancer Harboring BRAF Alterations |
|---|---|
| Brief Title | FORTE: FORE8394 in Participants With Cancer Harboring BRAF Alterations |
| Sponsor | FORE Biotherapeutics, Inc. |
| Study Type | Interventional (Clinical Trial) |
| Phase | Phase 2 |
| Design | Master Protocol / Basket Trial - 4 Sub-Protocols |
| Status | Recruiting |
| Enrollment Target | ~125 participants |
| Tumor Category | N | ORR | 95% CI | Median DoR |
|---|---|---|---|---|
| Primary CNS V600 (MAPKi-naive) | 9 | 66.7% | [29.9-92.5] | 13.9 mo (3.7-32.3) |
| - Low-grade glioma/Glioneuronal | -- | -- | -- | mPFS: Not Reached |
| - High-grade glioma (Grade 3-4) | -- | -- | -- | mPFS: 6.7 mo |
| Other Solid Tumors V600 | 24 | 41.7% | -- | 17.8 mo (3.7-59.2) |
| Sub-Protocol | Population | Target N | Response Criteria |
|---|---|---|---|
| A CNS Tumors | BRAF V600 Primary CNS Tumors (recurrent/progressive) | ~50 | RANO |
| B Solid Tumors | Other BRAF V600 Solid Tumors | ~25 | RECIST v1.1 |
| C Rare Tumors | Rare BRAF V600 Tumors (≤40,000 US patients/yr) | ~25 | RECIST v1.1 |
| D BRAF Fusions | BRAF Class 2 Fusions | ~25 | RECIST v1.1 |
| Drug | Plixorafenib (FORE8394 / PLX8394) |
|---|---|
| Dose | 900 mg QD (once daily, continuous) |
| PK Booster | Cobicistat (in some cohorts) |
| Route | Oral |
| Mechanism | Novel BRAF inhibitor - Dimer and Paradox Breaker. Disrupts RAF dimerization, prevents paradoxical activation. Targets both Class 1 (V600) mutations and Class 2 (fusions). |
| Key Advantage | No MEK inhibitor combination required |
| Common TEAEs | Severity | Grade 3+ |
|---|---|---|
| LFT Elevations (ALT/AST) | Grade 1-2 | Rare |
| Fatigue | Grade 1 | 0% |
| Nausea | Grade 1 | 0% |
| Diarrhea | Grade 1 | 0% |
| Vomiting | Grade 1 | 0% |
| Headache (CNS patients) | Variable | <5% |
| Fast Track | Granted September 2022 - Treatment of cancers harboring BRAF Class 1 (V600) and Class 2 alterations who have exhausted prior therapies |
|---|---|
| Orphan Drug | Granted March 2023 - Treatment of primary brain and CNS malignancies |
| Approval Pathway | Accelerated Approval based on ORR and Duration of Response |
| Confirmatory Trial | Phase 3 design in planning |
| Total Sites | 54 activated |
|---|---|
| Countries | 9 countries (Global trial) |
| Status | Recruiting |
| Type | Endpoint | Assessment |
|---|---|---|
| Primary | Overall Response Rate (ORR) | BICR per RECIST v1.1 (solid) or RANO (CNS) |
| Primary | Duration of Response (DoR) | Time from first response to progression |
| Secondary | Progression-Free Survival (PFS) | -- |
| Secondary | Overall Survival (OS) | -- |
| Secondary | Safety and Tolerability | AE monitoring, lab assessments |