FORTE Clinical Brief — External Update

Registrational Phase 2 basket study of plixorafenib (FORE8394) · Protocol PLX-120-03 · Synthesized from Fore press releases, ClinicalTrials.gov, JCO TPS2091, and third-party coverage (external search, June 2026).
NCT05503797 Recruiting Registration-intended Bayesian adaptive basket BTD Apr 2026
Executive summary. The lead registrational path is Sub-protocol B (recurrent/progressive BRAF V600 primary CNS tumors). A pre-specified interim (n=25) passed in Sept 2025 — IDMC recommended continue-as-planned on BICR ORR, but no public registrational topline ORR has been released. Topline CNS basket data expected H2 2026; company has cited accelerated-approval NDA if efficacy/safety sufficient. FDA Breakthrough Therapy Designation for BRAF V600E high-grade glioma granted April 2026.
254
Est. enrollment (CT.gov)
70
Active sites · 12 countries
H2 '26
CNS topline expected
Jun '26
Primary completion (est.)

📅 Catalyst timeline (external sources)

✓
Jun 2025
Phase 1/2a CeD-positive CeD-style readout (supporting)
✓
Apr 2025
AACR: ctDNA ↓ 85%; FORTE TIP poster
✓
Sep 2025
CNS interim n=25 passed
✓
Sep 2025
ATA thyroid Phase 1/2a data
✓
Apr 2026
FDA BTD (V600E HGG)
⌛
H2 2026
CNS registrational topline
?
TBD
Fusion & rare-solid interims
?
TBD
Accelerated-approval NDA

📊 Sub-protocol map (authoritative: JCO TPS2091 + CT.gov)

Note: Earlier internal dashboards labeled cohorts A–D differently. External registry and JCO poster use the mapping below.
Sub-protocolPopulationPlanned NInterim planPrimary endpointRegistrational status
A Advanced solid + primary CNS tumors with BRAF fusions ~100 n=25, n=50 ORR (BICR) Monotherapy indication · interim pending
B BRAF V600 recurrent/progressive primary CNS (HGG, LGG, glioneuronal, etc.) ~50 n=25 passed Sep 2025 ORR (BICR) · RANO Lead registrational basket · topline H2 2026
C Rare BRAF V600 advanced non-CNS solid tumors (incl. select thyroid/ATC) ~75 n=25, n=50 ORR (BICR) Monotherapy indication · interim pending
D BRAF V600 melanoma / thyroid (PK-focused; exploratory) ~12 None planned Intra-patient PK Exploratory · not registration-primary

📈 Clinical data updates (external)

DateSourceData typeKey findingsFORTE registrational?
Sep 24, 2025 Fore PR FORTE Sub-B interim (n=25) IDMC: continue as planned; met pre-specified efficacy threshold on BICR ORR; tumor regressions observed; ORR % not disclosed Yes — interim
Apr 2026 Fore PR Regulatory BTD for adult BRAF V600E-mutated recurrent/progressive HGG; cites Phase 1/2a + ongoing FORTE CNS data; reiterates topline by end 2026 Regulatory catalyst
Sep 2025 ATA 2025 Phase 1/2a thyroid (n=21) mPFS 63.9 mo; CBR 85.7% (MAPKi-naïve); durable control in PTC/ATC Supporting only
Apr 2025 AACR 2025 Biomarker / TIP V600E ctDNA MAF decreased in 85% of patients; PD in tumor biopsies; FORTE master-protocol poster (CT247) Exploratory / design
ASCO/SNO 2023 Conference (cited in 2026 BTD PR) Phase 1/2a CNS subgroup MAPKi-naïve BRAF V600 primary CNS: ORR 67% (n=9); CBR >75%; mDOR 13.9 mo Supporting only

Phase 1/2a — supporting efficacy (NCT02428712)

PopulationnORROther
MAPKi-naïve BRAF V600 primary CNS967%CBR >75%; mDOR 13.9 mo
MAPKi-naïve BRAF V600 (all types)—42%mDOR 17.8 mo; CBR >70%
Thyroid PTC/ATC (ATA 2025)21—mPFS 63.9 mo; CBR 85.7%

Drug-related discontinuation <2% cited in Phase 1/2a. Not a substitute for FORTE registrational topline.

FORTE registrational — what is / isn't public

  • Public: Sub-B interim passed at n=25; trial continues to ~50 CNS patients
  • Not public: Registrational ORR, DOR, PFS, OS from FORTE baskets
  • Not announced: Interim outcomes for Sub-A (fusions) or Sub-C (rare V600 solids)
  • Company path: Accelerated approval NDA for CNS basket if H2 2026 data support
  • Exploratory: Longitudinal ctDNA across all sub-protocols

🏥 Regulatory & designations

DesignationDetailDate
Fast TrackBRAF Class 1 (V600) and Class 2 alterations after prior therapies exhaustedSep 2022
Orphan DrugPrimary brain and CNS malignanciesMar 2023
Breakthrough TherapyAdult BRAF V600E-mutated recurrent/progressive high-grade gliomaApr 2026
Intended approval pathAccelerated approval on ORR + DOR (CNS basket); confirmatory Phase 3 in planning per company commentary—

🌐 Trial operations (ClinicalTrials.gov, Jun 2026)

Protocol

F8394-201 · PLX-120-03
Open-label parallel basket
Ages ≥10 (Sub-D: 18–65)
Weight ≥30 kg

Assessment

Primary: BICR ORR (A/B/C)
CNS: RANO · Solid: RECIST v1.1
Secondary: DOR, PFS, OS, DCR, safety

Governance

IDMC with pre-specified Bayesian interim rules
IPD sharing planned post-publication
DMC oversight ongoing

🔬 Implications for Fore Clinical Data Agentic Platform

Near-term analytic priorities

  • Sub-B CNS: RANO adjudication, pseudoprogression, BICR vs investigator concordance
  • ctDNA longitudinal response vs imaging (AACR 2025 signal: 85% MAF reduction)
  • Interim vs final topline reconciliation when H2 2026 data drop
  • Sub-A / Sub-C interim readiness (fusion partner, rare-tumor heterogeneity)

Data package status

  • PLX-120-03 dashboard reflects Phase 1/2a + interim milestone — update on topline
  • Correct sub-protocol labels A=fusions, B=CNS V600 (lead), C=rare solid, D=PK
  • Registrational ORR remains TBD until company disclosure
  • BTD supports regulatory narrative; does not replace registrational efficacy readout

📚 External sources cited

FORTE Clinical Brief v1 · External search synthesis · June 2026 · Not investment or medical advice · For Fore Biotherapeutics internal / partner use
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