NSCLC
Conditions
Brief 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.
Interventions
DRUGBEBT-109
BEBT-109 is based on the 3+3 model, with a dose ascent starting from 120mg qd
Sponsors
Hunan Province Tumor Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | 2 years | Defined as one of adverse events defined by NCI CTCAE V5.0 from the first day to the 28th day of the treatment period. |
| MTD | 2 years | If only 1 of 3 participants in a dose group has DLT, 3 additional subjects in this group will be tested at the same dose level; If no participants developed DLT, the next dose study was conducted; If 2 of the first 3 participants developed DLT or 2 of 6 participants developed DLT, the previous dose of the dose was the maximum tolerated dose (MTD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 2 years | Defined as the proportion of subjects in complete remission (CR) and partial remission (PR) to the total subjects |
| DCR | 2 years | Defined as the proportion of subjects with complete remission (CR), partial remission (PR) and stable disease (SD) to the total subjects |
Countries
China
Outcome results
None listed