Glossary for FRED

A kinase in the MAPK (RAS-RAF-MEK-ERK) growth-signaling pathway. Activating BRAF alterations drive many cancers and are the target of plixorafenib.

The most common activating point mutations at codon 600. They signal as active monomers and define sub-protocols A–C of the trial.

A functional grouping of BRAF alterations: Class 1 = V600 monomers; Class 2 = activating dimers (incl. fusions), RAS-independent; Class 3 = kinase-impaired, RAS-dependent. Response to RAF inhibitors differs by class.

A gene rearrangement that fuses BRAF's kinase domain to a partner, producing a constitutively active dimer. The focus of sub-protocol D; common in pediatric low-grade glioma.

The RAS → RAF → MEK → ERK signaling cascade that controls cell growth. BRAF alterations switch it on constitutively.

How BRAF signals: V600 mutants act as active monomers; Class 2/3 and fusions act as dimers. First-generation BRAF inhibitors work on monomers but can paradoxically activate dimers.

When a first-generation BRAF inhibitor bound to one protomer of a RAF dimer transactivates the other, increasing MAPK signaling in some cells — the cause of class-effect toxicities (rash, secondary skin tumors).

A patient not previously treated with a MAPK-pathway inhibitor (BRAF/MEK). The trial's strongest CNS response signal is in the MAPKi-naive setting.

Central-nervous-system tumors (e.g. gliomas). A priority population here — sub-protocol A — supported by Orphan Drug designation.

A slower-growing brain tumor, frequently BRAF-fusion driven in children — the basis of the pediatric signal.

Fore Biotherapeutics' investigational next-generation BRAF inhibitor — the agent under study in PLX-120-03.

A RAF inhibitor designed not to cause paradoxical MAPK activation — so it can be given as monotherapy without a MEK inhibitor to suppress the paradox, with less rash/fever.

Because plixorafenib does not drive the paradox, it does not require the MEK-inhibitor combination that class-effect BRAF drugs use — simpler regimen, distinct tolerability.

Treating by molecular alteration (BRAF) across many tumor histologies rather than one organ — the design principle of the FORTE basket.

The pivotal Phase 1/2 master-protocol study of plixorafenib in BRAF-altered cancers.

The ClinicalTrials.gov registration number for the FORTE / PLX-120-03 study.

One protocol with several parallel sub-studies (here sub-protocols A–D) sharing infrastructure and endpoints, split by BRAF alteration and tumor type.

A: CNS V600 tumors · B: solid-tumor V600 · C: rare V600 tumors · D: BRAF fusions (Class 2).

The Phase 1 stage that finds the dose, and the Recommended Phase 2 Dose carried forward. The trial reports 0 DLTs at RP2D.

A protocol-defined severe toxicity used to set the maximum tolerated / recommended dose.

The fraction of patients with a confirmed tumor shrinkage (CR + PR). A primary efficacy endpoint (e.g. 66.7% CNS ORR, MAPKi-naive).

Complete Response (tumor gone) / Partial Response (meaningful shrinkage) — the response categories that make up ORR.

Duration of Response and its median — how long responses last (e.g. 13.9-month median DoR in CNS). A co-primary for accelerated approval.

Disease Control Rate (CR+PR+stable disease) and Clinical Benefit Rate — broader benefit measures (>75% clinical benefit reported).

The standard imaging criteria for measuring solid-tumor response — used for the non-CNS sub-protocols.

Response Assessment in Neuro-Oncology — the CNS-specific response criteria used for brain tumors (sub-protocol A).

Using RANO for CNS and RECIST v1.1 for solid tumors within one basket, so each tumor type is measured appropriately.

Blinded Independent Central Review — an off-site expert panel that re-reads scans to confirm response objectively, key for a registrational endpoint.

The central lab that standardizes and QCs trial imaging; BTIP = the brain-tumor imaging protocol (3D T1W + FLAIR) with 91.5% compliance.

An FDA pathway to approve on a surrogate (ORR + mDoR) ahead of survival data, with confirmatory follow-up. The trial's regulatory target.

FDA designations that speed development (Fast Track, Sept 2022, BRAF Class 1&2) and support rare-disease programs (Orphan Drug, Mar 2023, primary CNS).

Next-generation sequencing — the molecular test that confirms a BRAF alteration for eligibility. Fusion-sensitive panels matter for Class 2 detection.

A defined group of patients within a sub-protocol (by alteration, tumor type, or dose) tracked together for safety and efficacy.

The full unit on the board: a goal/hypothesis with rationale, evidence, in-silico + clinical strategy, and its own discussion.

Lighter cards — an open ask, or a testable belief — that can be promoted into a full study later.

A badge for where the evidence points: supports / mixed / opposes / untested. Rolled up into the board's consensus meter.

A separate high / med / low grade for how sure we are — independent of stance.

Two views of the same studies; Board is a drag-to-move Kanban across idea → scoped → running → done.

Live avatars of who is on the board right now; click one to jump to the study they are viewing.