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DRUG:

lifirafenib (BGB-283)

i
Other names: BGB-283, BeiGene-283, BGB 283, BGB283, Beigene283, Beigene 283
Company:
BeiGene
Drug class:
EGFR inhibitor, pan-RAF inhibitor
Related drugs:
25d
Phase classification
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NRAS (Neuroblastoma RAS viral oncogene homolog)
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NRAS mutation
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mirdametinib (PD-0325901) • lifirafenib (BGB-283)
29d
Phase classification
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KRAS (KRAS proto-oncogene GTPase) • RAS (Rat Sarcoma Virus)
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KRAS mutation • NRAS mutation • RAS mutation
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lifirafenib (BGB-283)
7ms
T cell-mediated tumor killing sensitivity gene signature-based prognostic score for acute myeloid leukemia. (PubMed, Discov Oncol)
A T-cell mediated killing sensitivity gene-based prognostic score TTKPI showed good accuracy in predicting survival in AML. TTKPI corresponded to functional and immunological features of the tumor microenvironment including checkpoint expression patterns and should be investigated for precision medicine approaches.
Journal • Gene Signature
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CD4 (CD4 Molecule)
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Tabrecta (capmatinib) • lifirafenib (BGB-283)
over1year
Study of the Safety and Pharmacokinetics of BGB-283 (Lifirafenib) and PD-0325901 (Mirdametinib) in Participants With Advanced or Refractory Solid Tumors (clinicaltrials.gov)
P1b, N=105, Recruiting, BeiGene | Trial completion date: Apr 2024 --> Feb 2026 | Trial primary completion date: Mar 2024 --> Sep 2025
Trial completion date • Trial primary completion date • Combination therapy • Metastases
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NRAS (Neuroblastoma RAS viral oncogene homolog)
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NRAS mutation
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mirdametinib (PD-0325901) • lifirafenib (BGB-283)
3years
Blockade of mutant RAS oncogenic signaling with a special emphasis on KRAS. (PubMed, Pharmacol Res)
This led to the development of sotorasib as a second-line treatment of KRAS mutant non-small cell lung cancer. Considerable effort also has been expended to develop MAP kinase and PI3-kinase pathway inhibitors as indirect RAS antagonists.
Review • Journal
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)
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KRAS mutation
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Lumakras (sotorasib) • Zarnestra (tipifarnib) • Krazati (adagrasib) • avutometinib (VS-6766) • pictilisib (GDC-0941) • buparlisib (AN2025) • belvarafenib (RG6185) • ulixertinib (BVD-523) • lifirafenib (BGB-283) • naporafenib (ERAS-254)
over4years
Molecular landscape of BRAF-mutant NSCLC reveals an association between clonality and driver mutations and identifies targetable non-V600 driver mutations. (PubMed, J Thorac Oncol)
"In BRAF-mutant NSCLC, clonality is higher in known functional mutations and may allow identification of VUS more likely to be oncogenic drivers. Our data indicate certain non-V600 mutations are responsive to MEK and BRAF inhibitors. This integration of genomic profiling and drug sensitivity may guide treatment for BRAF-mutant NSCLC."
Journal
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF mutation • BRAF G469V • BRAF D594G • BRAF L597R • BRAF L597
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Guardant360® CDx
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Mekinist (trametinib) • Tafinlar (dabrafenib) • lifirafenib (BGB-283) • naporafenib (ERAS-254)
over4years
RAF dimer inhibition enhances the antitumor activity of MEK inhibitors in K-RAS mutant tumors. (PubMed, Mol Oncol)
Here, we report that the RAF dimer inhibitors, lifirafenib (BGB-283) and Compound C, show a strong synergistic effect with MEK inhibitors (MEKi), including mirdametinib (PD-0325901) and selumetinib, in suppressing the proliferation of K-RAS-mutated non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) cell lines. This synergistic effect was not observed with the B-RAF selective inhibitor, vemurafenib...A pharmacodynamic analysis supported a role for the synergistic phospho-ERK blockade in enhancing the antitumor activity observed in the K-RAS mutant models. These findings support a vertical inhibition strategy in which RAF dimer and MEK inhibitors are combined to target K-RAS-mutated cancers, and has led to a Phase 1b/2 combination therapy study of lifirafenib and mirdametinib in solid tumor patients with K-RAS mutations and other MAPK pathway aberrations.
Journal
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KRAS (KRAS proto-oncogene GTPase) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase)
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KRAS mutation
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Zelboraf (vemurafenib) • Koselugo (selumetinib) • mirdametinib (PD-0325901) • lifirafenib (BGB-283)
over4years
Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors. (PubMed, J Clin Oncol)
Lifirafenib is a novel inhibitor of key RAF family kinases and EGFR, with an acceptable risk-benefit profile and antitumor activity in patients with B-RAF-mutated solid tumors, including melanoma, PTC, and LGSOC, as well as K-RAS-mutated NSCLC and endometrial carcinoma. Future comparisons with first-generation B-RAF inhibitors and exploration of lifirafenib alone or as combination therapy in patients with selected RAS mutations who are resistant/refractory to first-generation B-RAF inhibitors are warranted.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation
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lifirafenib (BGB-283)