KEY TAKEAWAYS
- The phase 2 trial aimed to assess the effectiveness of combining becotarug and osimertinib in treating EGFR ex20ins positive NSCLC patients.
- The combination of becotarug and osimertinib showed manageable safety and significant anti-tumor effects in EGFR ex20ins mutation-positive NSCLC patients.
Patients with EGFR exon 20 insertion (ex20ins)-positive non small cell lung cancer (NSCLC) have limited treatment options and a poor prognosis. Becotarug, a monoclonal antibody targeting EGFR, demonstrated promising efficacy in a previous phase 1b study.
Li Zhang and the team sought to study the combined efficacy of becotarug and osimertinib for EGFR ex20ins-positive NSCLC patients.
This multicenter phase 2 trial enrolled advanced NSCLC patients with EGFR ex20ins mutations after failing platinum chemotherapy. Patients received becotarug (6 mg/kg bi-weekly) plus osimertinib (160 mg daily) until disease progression by independent review, intolerable toxicity, or withdrawal. The primary objective assessed the combination’s efficacy; secondary objectives included safety, pharmacokinetics, and immunogenicity.
Between November 26, 2021, and June 21, 2023, about 126 patients, with a median age of 59 years (range 34-82 years), were enrolled. Of the 112 patients included in the intention-to-treat (ITT) population (defined as patients with EGFR ex20ins confirmed by central lab), 89% (n=100) experienced tumor shrinkage according to independent review committee (IRC) assessment.
The confirmed objective response rate (ORR) per IRC was 50% (95% CI, 40-60%) with a 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 patients (99%), with 99 patients (79%) experiencing TRAEs of grade 3 or higher. The most common TRAEs were rash (80%), diarrhea (68%), decreased appetite (64%), oral mucositis (65%), and weight loss (59%), mostly of low grade, with corresponding rates of grade 3 or higher of 32%, 10%, 4%, 11%, and 2%, respectively. Most TRAEs were EGFR target-related toxicities that could be managed well, with only 5% of patients permanently discontinuing treatment due to TRAEs.
The combination of becotarug and osimertinib demonstrated manageable safety and notable antitumor efficacy in patients with EGFR ex20ins-positive NSCLC.
The trial was sponsored by the Shanghai JMT-Bio Inc.
Source: https://rb.gy/47cl4n
Clinical Trial: https://clinicaltrials.gov/study/NCT05132777
Li Z, Fang W, Zhao S, et al. (2024) “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).” Presented at ELCC 2024 (Abstract 137MO).
