- |||||||||| CLN-081 / Cullinan Oncology, Otsuka
Phase (Ph) 1/2a study of CLN-081 in patients (pts) with NSCLC with EGFR exon 20 insertion mutations (Ins20). (Available On Demand) - Apr 28, 2022 - Abstract #ASCO2022ASCO_2934; P1/2 In pts with heavily-pretreated advanced EGFR ins20 NSCLC, CLN-081 has a manageable safety profile, with anti-tumor activity across the range of doses tested. Further, CLN-081 has demonstrated a favorable clinical profile at the dose of 100 mg BID, with an encouraging objective response rate, response durability, and no Gr 3 rash or diarrhea.
- |||||||||| BLU-451 / Blueprint Medicines
LNG-451, a potent inhibitor of EGFR exon 20 insertion mutations with high CNS exposure (Section 26) - Mar 9, 2022 - Abstract #AACR2022AACR_5382; An ex vivo imaging analysis of the brain and spinal cords from all animals at the end of the study showed a dose-dependent decrease in the bioluminescent signal in both brain and spinal cords from mice treated with LNG-451 relative to the vehicle control animals. Taken together, LNG-451 is a CNS-penetrant, wild-type EGFR-sparing, EGFR Ex20ins inhibitor that is expected to provide strong anti‑tumor efficacy for patients with advanced/metastatic solid cancers harboring oncogenic EGFR exon 20 insertions with reduced WT EGFR driven toxicities.
- |||||||||| ORIC-114 / ORIC Pharma, Voronoi
ORIC-114, an orally bioavailable, irreversible kinase inhibitor, has superior brain penetration and antitumor activity in subcutaneous and intracranial NSCLC models (Section 26) - Mar 9, 2022 - Abstract #AACR2022AACR_5368; In this subcutaneous model, ORIC-114 was superior to CLN-081 in efficacy and tolerability, and superior to BDTX-189 in efficacy...Once daily oral administration of ORIC-114 significantly regressed established intracranial NSCLC tumors and demonstrated greater efficacy than TAK-788, commensurate with the superior brain exposure of ORIC-114...Taken together, these data confirm ORIC-114 as a potent, selective, irreversible, brain penetrant exon 20 inhibitor, and a promising therapeutic candidate, including for patients with CNS metastases. Based upon these data, ORIC-114 is entering a Phase 1/1b clinical trial in genetically defined cancers.
- |||||||||| BLU-451 / Blueprint Medicines
LNG-451 is a potent, CNS-penetrant, wild-type EGFR sparing inhibitor of EGFR exon 20 insertion mutations (Section 26) - Mar 9, 2022 - Abstract #AACR2022AACR_5366; LNG-451 potently suppressed EGFR phosphorylation in tumor tissue (e.g. 99%, 3 h post 50 mg/kg dose) but had minimal-to modest suppression of phospho-EGFR in large intestine tissue (e.g. 4.2%, 3h post 50 mg/kg dose) and skin tissue (e.g 1.9%, 3h post 50 mg/kg dose). Taken together, LNG-451 is a wild-type EGFR-sparing, CNS-penetrant EGFR Ex20ins inhibitor that is expected to provide strong anti‑tumor efficacy for patients with advanced/metastatic solid cancers harboring oncogenic EGFR exon 20 insertions with reduced WT EGFR-driven toxicities.
- |||||||||| zipalertinib (CLN-081) / Cullinan Therap, Otsuka
Trial primary completion date, EGFR exon 20, Metastases: REZILIENT1: A Phase 1/2 Trial of CLN-081 in Patients with Non-Small Cell Lung Cancer (clinicaltrials.gov) - Nov 18, 2021 P1/2, N=80, Recruiting, Here, we discuss the mechanisms of EGFR-TKIs resistance induced by secondary EGFR mutations, highlight the development of targeted drugs to overcome EGFR mutation-mediated resistance, and predict the promising directions for development of novel candidates. Trial primary completion date: Sep 2021 --> Mar 2022
- |||||||||| CLN-081 / Cullinan Oncology
CLN-081 (TAS6417) (STARLIGHT BALLROOM) - Feb 21, 2020 - Abstract #IASLCLCTT2020IASLC_LCTT_59;
- |||||||||| Completely agree, look data for poziotinib, nazartinib, pyrotinib, TAS6417, TAK788, tarloxotinib, luminespib, WZ8040, WZ4002, and profound data around combos (Twitter) - Oct 10, 2019
|