137MO - Phase II study of becotarug (JMT101) combined with osimertinib in patients (pts) with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion (ex20ins) mutations (BECOME study)

Background

Pts with EGFR ex20ins positive NSCLC have limited therapeutic options and dismal prognosis. Becotarug is a humanized IgG1 monoclonal antibody targeting EGFR. Becotarug combined with osimertinib has shown encouraging efficacy in our previous phase Іb study (Zhao et al. Nature Communications; 2023). Here we report the results of a phase II study of Becotarug combined with osimertinib in this setting (NCT05132777).

Methods

This is a multicenter open-label, phase II study. Pts with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations, who had failed prior platinum-based chemotherapy, were enrolled. Eligible pts were treated with Becotarug (6 mg/kg Q2W) combined with osimertinib (160 mg QD) until IRC-assessed disease progression, intolerance of toxicity, withdrawal, whichever came first. The primary objective was to determine the efficacy of Becotarug combined with osimertinib. Secondary objectives included safety, pharmacokinetics and immunogenicity.

Results

Between November 26, 2021, and June 21, 2023, 126 pts with a median age of 59 years (range 34-82 years) were enrolled. Among the 112 pts included in the ITT (defined as pts with EGFR ex20ins confirmed by central lab), 89% of patients (n=100) experienced tumor shrinkage by IRC assessment. The confirmed objective response rate (ORR) per IRC was 50% (95%CI, 40-60%) with the disease control rate (DCR) of 80% (95% CI, 71-87%). Notably, the ORR in patients with brain metastases was 43% (18/42, 95% CI, 28-59%). Treatment-related adverse events (TRAEs) were reported in 125 pts (99%), of whom, 99 pts (79%) reported ≥ Grade 3 TRAEs. The most common TRAEs were rash (80%), diarrhea (68%), decreased appetite (64%), oral mucositis (65%) and weight decreased (59%), but mostly low in grade, with corresponding ≥ Grade 3 rates of 32%, 10%, 4%, 11% and 2%, respectively. Most TRAEs were EGFR target-related toxicities that can be well managed, with only 5% of pts discontinued permanently due to TRAEs.

Conclusions

Becotarug in combination with osimertinib showed manageable safety and compelling antitumor activity in pts with NSCLC harboring EGFR ex20ins mutations.

Clinical trial identification

NCT05132777.

Legal entity responsible for the study

Shanghai JMT-Bio Technology Co., Ltd.

Funding

Shanghai JMT-Bio Technology Co., Ltd.

Disclosure

J. Hao, X. Wan, M. Li, Y. Yang, X. Yang: Financial Interests, Institutional, Full or part-time Employment: CSPC Pharmaceutical Group Limited. All other authors have declared no conflicts of interest.