OncoSignal
Live from Open Targets Platform, fetched 2026-11-12 09:25 UTC. Every row links to its source record.

ARAF A-Raf proto-oncogene, serine/threonine kinase

ENSG00000078061 · protein coding · Open Targets profile

Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade. Phosphorylates PFKFB2 (PubMed:36402789). .

1 of the 3 drugs recorded against ARAF is approved

Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.

1 small molecule drug at Approved: TOVORAFENIB1 small molecule drug at Phase 2: BELVARAFENIB1 small molecule drug at Phase 1: LY-3009120Small molecule 3Approved 1Phase 2 1Phase 1 1

Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.

In 13 of 15 cancers, the evidence for ARAF comes mainly from mutations found in tumours

Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.

Inherited (germline) variantsMutations in tumours (somatic)
00.250.50.751low grade gliomalow grade gliomagliomagliomacolorectal adenocarcinomacolorectal adenocarcinomacolorectal adenocarcinoma: somatic 0.30lung adenocarcinomalung adenocarcinomalung adenocarcinoma: somatic 0.28small cell lung carcinomasmall cell lung carcinomasmall cell lung carcinoma: somatic 0.27melanomamelanomamelanoma: somatic 0.30lung carcinomalung carcinomalung carcinoma: somatic 0.30urinary bladder carcinomaurinary bladder carcinomaurinary bladder carcinoma: somatic 0.30pancreatic ductal adenocarcinomapancreatic ductal adenocarcinomapancreatic ductal adenocarcinoma: somatic 0.30hepatocellular carcinomahepatocellular carcinomahepatocellular carcinoma: somatic 0.30non-small cell lung carcinomanon-small cell lung carcinomanon-small cell lung carcinoma: somatic 0.30acute myeloid leukemiaacute myeloid leukemiaacute myeloid leukemia: somatic 0.30head and neck squamous cell carcinomahead and neck squamous cell carcinomahead and neck squamous cell carcinoma: somatic 0.30thyroid gland papillary carcinomathyroid gland papillary carcinomathyroid gland papillary carcinoma: somatic 0.30B-cell chronic lymphocytic leukemiaB-cell chronic lymphocytic leukemiaB-cell chronic lymphocytic leukemia: somatic 0.30

Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.

Tractability

Small molecule
Advanced Clinical, Structure with Ligand, High-Quality Ligand, Druggable Family
Antibody
Human Protein Atlas loc
PROTAC
Database Ubiquitination, Half-life Data, Small Molecule Binder

gnomAD loss of function constraint: o/e 0.37474000453948975 (upper bound 0.5556899905204773). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.

Who runs trials of these drugs

Principal investigators and study chairs on 17 registry trials, updated in the last three years, of the most advanced drugs against ARAF (tovorafenib, belvarafenib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.

3 of 15 trials of drugs against ARAF have sites only in United States

Registry trials of tovorafenib, belvarafenib updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 7 of 15 have all sites in one country.

Sites only in this groupSites here and elsewhere
United StatesUnited States: 3 trials with sites only hereUnited States: 8 trials with sites here and elsewhere11ChinaChina: 0 trials with sites only hereChina: 1 trials with sites here and elsewhere1EuropeEurope: 0 trials with sites only hereEurope: 5 trials with sites here and elsewhere5JapanJapan: 1 trials with sites only hereJapan: 1 trials with sites here and elsewhere2OtherOther: 3 trials with sites only hereOther: 8 trials with sites here and elsewhere11

Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 2 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.

4 trials of drugs against ARAF were stopped early

Terminated, withdrawn and suspended interventional trials of tovorafenib, belvarafenib, LY-3009120, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 4 most recent of 4.

  • Ph2NCT04985604briefwhy it stopped
    terminated · 2025-10-02 · Day One Biopharmaceuticals, Inc. · Tovorafenib
    “Sponsor decision”
  • Ph1NCT07121829briefwhy it stopped
    terminated · 2025-08-14 · Day One Biopharmaceuticals, Inc. · Tovorafenib, Tovorafenib Drug: Pimasertib
    “Sponsor decision”
  • Ph1NCT02723006briefwhy it stopped
    terminated · 2024-03-05 · Millennium Pharmaceuticals, Inc. · matched by the registry's drug synonyms
    “Business decision: Protocol efficacy futility met”
  • Ph1NCT02014116briefwhy it stopped
    terminated · 2019-12-27 · Eli Lilly and Company · matched by the registry's drug synonyms
    “This trial was terminated early based on the lack of sufficient clinical efficacy observed.”
Paediatric incentives and obligations for ARAF's drugs

For tovorafenib, belvarafenib, LY-3009120: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.

  • FDA pediatric target list: no · ARAF is not on the list
    Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
  • EU paediatric investigation plan: yes · EMEA-002763-PIP01-20-M01 (tovorafenib, Treatment of paediatric low grade glioma): PM: decision on the application for modification of an agreed PIP, 27 Oct 2023
    Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-002763-PIP01-20-M01, 2026-11-11
  • EU orphan designation: yes · EU/3/21/2434 positive 20 May 2021: Treatment of glioma
    Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA EU/3/21/2434, 2026-11-11
  • Authorised in the EU: yes · Ojemda: authorised since 20 Apr 2026, orphan medicine, conditional
    Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA EPAR Ojemda, 2026-11-11
  • FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link
    Rule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
  • FDA pediatric oncology approval: yes · Tovorafenib [Ojemda], 23 Apr 2024: Treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation
    Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
  • Registered studies open to children: yes · 11 interventional studies of tovorafenib, belvarafenib, ly-3009120 include patients under 18; 8 are recruiting, not yet recruiting or active
    Rule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12

Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs

All 3 drugs and clinical candidates as a table

Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.

DrugTypeHighest stageIndicationsSource records
TOVORAFENIBSmall moleculeapprovalglioma, low grade glioma, melanoma, neoplasm, craniopharyngioma, Langerhans cell histiocytosis, diffuse intrinsic pontine glioma, malignant glioma, +1 moreOpen Targets · ChEMBL
BELVARAFENIBSmall moleculephase 2central nervous system neoplasm, central nervous system cancer, melanomaOpen Targets · ChEMBL
LY-3009120Small moleculephase 1cancerOpen Targets · ChEMBL