BLU-701

Advanced inhibitors, including BBT-176, BLU-945, and BLU-701, have effectively targeted resistant mutations and reduced disease progression. Such combination regimens aim to optimize PFS, OS, and ORR while minimizing adverse effects and addressing the limitations of current therapies. This study explores the landscape of EGFR mutations, their clinical significance, and the integration of innovative fourth-generation EGFR-TKIs with immunotherapies, emphasizing the potential of precision medicine in advancing the management of EGFR-mutated NSCLC.

P1/2, N=20, Terminated, Blueprint Medicines Corporation | N=160 --> 20 | Trial completion date: Dec 2024 --> Dec 2022 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Dec 2022; Lack of efficacy

P1/2, N=160, Active, not recruiting, Blueprint Medicines Corporation | Recruiting --> Active, not recruiting

The in vivo antitumor activities of BLU-945 and BLU-701 as single agents suggest both BLU-945 and BLU-701 have the potential to be used as 1L therapy in patients with EGFR L858R-driven NSCLC. The superior in vivo antitumor activity of BLU-945 or BLU-701 in combination with osimertinib in prolonging the DOR or increasing tumor growth inhibition in these models may have clinical application in improving outcomes of patients with EGFR L858R-driven NSCLC in 1L settings.

Consistent with its brain penetration properties, BLU-701 exhibited dose-dependent brain tumour inhibition that surpassed gefitinib and erlotinib in an EGFR ex19del PC9-luc CDX model in which cells were implanted intracranially or inoculated in the carotid artery (followed by migration to the brain). The in vivo activity of BLU-701 supports its potential as a treatment for patients with EGFR-mutated NSCLC, including those with the C797S mutation resistant to covalent 3rd-generation TKIs, such as osimertinib. Its intracranial penetrance and brain tumour response suggest potential benefits in treating and/or preventing brain metastases. Broader EGFR mutational coverage could be achieved with BLU-701 and BLU-945 in combination, which could potentially prolong responses.

P1/2, N=160, Recruiting, Blueprint Medicines Corporation | Not yet recruiting --> Recruiting

P1/2, N=160, Not yet recruiting, Blueprint Medicines Corporation