The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to mobocertinib (TAK-788; Takeda) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

Mobocertinib is a small-molecule tyrosine kinase inhibitor (TKI) designed to selectively target EGFR and human EGFR 2 (HER2) exon 20 insertion mutations. The designation is supported by data from an ongoing multicenter, open-label phase 1/2 trial evaluating the efficacy and safety of mobocertinib 160mg once daily in patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations and have been previously treated with systemic chemotherapy. 

Findings from the study showed that treatment with mobocertinib resulted in a median progression-free survival (PFS) of 7.3 months and a confirmed overall response rate (ORR) of 43% (n=12/28) in patients with locally advanced or metastatic EGFR exon 20 insertion-mutant NSCLC, including those with brain metastases at baseline. Additionally, mobocertinib demonstrated a disease control rate of 86% (n=24/28) for the total patients treated and 100% for patients without brain metastases at baseline (n=16/16).

With regard to safety, the most common treatment-related adverse events were diarrhea (85%), nausea (43%), rash (36%), vomiting (29%) and decreased appetite (25%).

“Although most EGFR mutations can be targeted by currently available TKIs, people with exon 20 insertion mutations often suffer and feel forgotten since available EGFR inhibitors don’t work well in their cancer,” said Jill Feldman, Lung Cancer Patient, Advocate, and Co-Founder of the EGFR Resisters. “We are excited by the potential this treatment has to extend the lives of people who have had no approved treatment options to target their disease.”

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The FDA previously granted Orphan Drug designation to mobocertinib for the treatment of lung cancer with HER2 mutations or EGFR mutations including exon 20 insertion mutations.

Mobocertinib will be evaluated in several lung cancer clinical trials including the phase 2 EXCLAIM and J-EXCLAIM studies and the phase 3 EXCLAIM-2 trial.

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