Nichole Tucker, MA, is the Web Editor for Targeted Oncology. Tucker received her Bachelor of Arts in Mass Communications from Virginia State University and her Master of Arts in Media & International Conflict from University College Dublin.
The Investigational New Drug Application for the novel EGFR tyrosine kinase inhibitor BBT-176 was cleared by the FDA for treatment of EGFR C797S–mutant non–small cell lung cancer, according to a press release from Bridge Biotherapeutics, Inc, developer of BBT-176.
The Investigational New Drug (IND) Application for the novel EGFR tyrosine kinase inhibitor (TKI) BBT-176 was cleared by the FDA for treatment ofEGFRC797Smutant non–small cell lung cancer (NSCLC), according to a press release from Bridge Biotherapeutics, Inc, developer of BBT-176.
“We are highly proud of the IND clearance of BBT-176, a novel EGFR-TKI inhibiting C797S mutations for NSCLC treatments, by the US FDA…Bridge will take the best-efficient development practices for bringing new treatment options for patients with NSCLC in need of novel therapy,” said James Lee, ceo of Bridge Biotherapeutics.1
Following the IND clearance, the company plans to initiate a dose-escalation study to find the maximum tolerated dose (MTD) of BBT-176. The dose-escalation phase will be the first part of a phase I/II first-in-human study in Korea, which will evaluate the safety, tolerability, and anti-tumor efficacy of the drug in patients with advanced NSCLC. A dose-expansion study will be the second part of the study, which will re-evaluate the safety, tolerability, and efficacy of the MTD of BBT-176 in patients in the United States and Korea.
The IND for BBT-176 was submitted in December of 2019 to address the need for other options for the treatment of patients with NSCLC who developed resistance to osimertinib (Tagrisso).
In a recent study on osimertinib resistance in patients withEGFR-mutant NSCLC, experts have determined that osimertinib resistance is inevitable in most patients. Resistance to osimertinib is considered to be highly heterogeneous, and therefore, encompassesEGFR-dependent andEGFR-independent mechanisms. The dependent mechanisms include mutations in T790M, C797S, G796, L792, L718, G719, G724, exon 20 as well asEGFRgene amplification. Independent mechanisms include MET geneamplification,PI3Kpathway activation, HER2amplification, RASMAPK pathway activation, cell-cycle gene alterations, oncogenic fusions, and histologic and phenotypic transformations. The study suggests that a sequential or alternating approach, adjusting the doses of EGFR TKIs, or combining 2 EGFR TKIs can be a strategy for treatingEGFR-mutant NSCLC.2
In pre-clinical studies, BBT-176 showed anti-tumor efficacy againstEGFRC797S triple mutations. It also demonstrated enhanced efficacy when combined with anti-EGFRantibodies.