antitumor activity and safety of bebt-109, a novel egfr inhibitor, in previously treated nsclc

Conditions: NSCLC

Summary: this clinical study was a first-in-human, phase 1b, single-center, single-arm, open-label, dose escalation and expansion trial that aimed to determine the safety, tolerability and efficacy of bebt-109 in patients with locally advanced or metastatic nsclc harboring egfr exon20ins mutations who had received at least one line of previous treatment.


Eligibility criteria:
inclusion criteria: * sign written informed consent before implementing any trial-related procedures; * age ≥18 years and no limit on the gender. * histologically or cytologically confirmed locally advanced or metastatic nsclc with egfr exon20ins mutation according to assessments made in local laboratories. * previous treatment and type of mutation: 1. disease progression in doses extension cases may have been treated with an egfr-tki (e.g., gefitinib, erlotinib, eclitinib, afatinib, or dapatinib) and prior written test reports confirming egfr t790m mutation. 2. disease progression after prior chemotherapy regimen and/or egfr-tki treatment in dose-extension cases, and prior written test reports confirming egfr 20 exon insertion mutations. 3. disease progression following prior chemotherapy regimen and/or egfr-tki treatment in dose-extension cases, and prior written test reports confirming other rare mutations in egfr (egfr g719a, l861q, or s768i point mutations). 4. patients who are intolerant to chemotherapy or egfr-tki and have no other effective treatment can also be admitted to the dose expansion group after judgment by the investigator. * eastern cooperative oncology group (ecog) performance status of 0-2. * patients with brain metastasis were only enrolled if the metastases were stable. * subjects had at least 1 measurable lesion that met the recist 1.1 criteria. * if female subjects are of childbearing potential, adequate contraception (e.g., condoms, etc.) should be used, no breastfeeding should be used, and a negative pregnancy test before administration should be given. exclusion criteria: * combined with any other malignancy (except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix). * genetic testing confirmed the presence of c-met amplification, her-2 amplification and kras mutations, and other genetic mutations that clearly confirm resistance to egfr-tki. * from the last treatment of egfr-tki (such as erlotinib, gefitinib, eclitinib, afatinib or osimertinib, etc.) to the first administration of this clinical trial, the interval is less than 14 days or 5 half-lives (whichever is longer is the exclusion criterion), and the specific drugs involved are decided by the investigator based on comprehensive consideration. * in the 4 weeks prior to the first administration of the study treatment, participants had used other anticancer drugs (including immune cell therapy) in the previous treatment regimen. * those who have not withdrawn from other clinical trials within 4 weeks prior to the first administration of the study treatment. * previous homogeneous drug restriction: 1. patients with egfr mutation previously treated with osimertinib or other third-generation egfr inhibitor drugs (eg, ivelitinib, emetinib, and eflotinib) ; 2. egfr exon20 insertion mutants have used drugs that target egfr 20 exon insertion mutants (e.g. poziotinib tarloxotinib tak788 jnj-61186372 cln-081, etc.) 3. other egfr rare mutations (egfr g719a, l861q, or s768i point mutations) have been treated with afatinib.