Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20...

Area of Science:

• Oncology
• Pharmacology
• Genetics

Background:

• Non-small cell lung cancer (NSCLC) often harbors epidermal growth factor receptor (EGFR) mutations.
• EGFR exon 20 insertions (EGFRex20ins) are a challenging subset of NSCLC with limited oral targeted therapy options.
• Mobocertinib is an oral EGFR inhibitor specifically designed to target EGFR mutations, including EGFRex20ins.

Purpose of the Study:

• To evaluate the safety and efficacy of mobocertinib in patients with advanced NSCLC harboring EGFRex20ins.
• To determine the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of mobocertinib.
• To assess the antitumor activity, including response rate and duration, and progression-free survival (PFS).

Main Methods:

• A phase I/II dose-escalation/expansion trial (ClinicalTrials.gov NCT02716116) was conducted.
• Dose escalation identified 160 mg/day as the RP2D and MTD.
• Efficacy was assessed in 28 patients with EGFRex20ins treated at 160 mg/day, evaluating confirmed response rate, duration of response, and PFS.

Main Results:

• The RP2D and MTD were determined to be 160 mg/day.
• Common treatment-related adverse events (TRAEs) included diarrhea (83%), nausea (43%), rash (33%), and vomiting (26%). Grade ≥3 diarrhea occurred in 21% of patients.
• Among 28 EGFRex20ins patients, the confirmed response rate was 43% (95% CI, 24%-63%), with a median duration of response of 14 months and median PFS of 7.3 months.

Conclusions:

• Mobocertinib demonstrated significant antitumor activity in patients with advanced NSCLC and EGFRex20ins.
• The safety profile was consistent with other EGFR inhibitors, with manageable toxicities.
• These findings support the continued development of mobocertinib for patients with EGFRex20ins NSCLC, addressing an unmet need for oral targeted therapies.