Takeda Pharmaceutical recently announced that the U.S. Food and Drug Administration (FDA) has accepted and granted priority review its New Drug Application (NDA) for the oral targeted cancer drug mobocertinib (TAK-788). This drug is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (mNSCLC) who have progressed on prior platinum-based therapy and whose disease is confirmed by an FDA-approved assay to be EGFR exon 20 insertion mutation positive (EGFRex20ins+).
Mobocertinib is the first oral therapy specifically targeting EGFR exon 20 insertion mutations. Currently, there are no approved targeted therapies for mNSCLC patients with EGFR exon 20 insertion mutations, and current treatment regimens offer limited benefit.
The mobocertinib NDA is based on the results of a Phase 1/2 clinical trial. This study is being conducted in patients with metastatic non-small cell lung cancer (mNSCLC) who have progressed on prior platinum-based therapy and carry EGFR exon 20 insertion mutations (EGFRExon20insertion+), and is evaluating the efficacy and safety of mobocertinib.
In late January of this year, Takeda presented the latest results of this study in an oral presentation at the 21st World Congress on Lung Cancer (WCLC) online conference hosted by the International Association for the Study of Lung Cancer in 2020. The data showed that mobocertinib demonstrated clinically meaningful antitumor efficacy: (1) the investigator-assessed objective response rate (ORR) was 35% (40/114; 95% CI: 26-45), and the independent review committee (IRC)-assessed ORR was 28% (32/114; 95% CI: 20-37). (2) Mobocertinib treatment demonstrated durable remission, with a median duration of response (DOR) of 17.5 months (95% CI: 7.4–20.3) as assessed by the IRC. (3) The median progression-free survival (PFS) confirmed by the IRC was 7.3 months (95% CI: 5.5–9.2), and the disease control rate (DCR) was 78% (89/114; 95% CI: 69–85).
The safety profile observed in the study was manageable. As of the data cutoff in May 2020, the most common treatment-related adverse events (TRAEs; ≥20%) in patients pretreated with platinum-based drugs were diarrhea (90%), rash (45%), paronychia (34%), nausea (32%), decreased appetite (32%), dry skin (30%), and vomiting (30%). Grade ≥3 TRAEs (≥5%) included diarrhea (21%). Nineteen patients (17%) discontinued treatment due to adverse events, the most common being diarrhea (4%) and nausea (4%). The safety profile as of November 2020 was consistent with that as of May 2020.
Approval History of the Small Molecule Tyrosine Kinase Inhibitor (TKI) mobocertinib
In 2019, the U.S. FDA granted mobocertinib Orphan Drug Designation (ODD) for the treatment of lung cancer patients with HER2-mutated or EGFR-mutated tumors (including exon 20 insertion mutations).
In April 2020, the U.S. FDA granted mobocertinib Breakthrough Therapy Designation for the treatment of metastatic non-small cell lung cancer (NSCLC) patients whose disease progressed during or after platinum-based chemotherapy and who harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations.
In October 2020, mobocertinib was granted Breakthrough Therapy Designation (BTD) for the same indication by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China.
