Antitumor Activity and Safety of BEBT-109, a Novel EGFR Inhibitor, in Previously Treated NSCLC
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BEBT-109 120mg BEBT-109 orally at an initial dose of 120 mg once daily. |
Drug: BEBT-109
BEBT-109 is based on the "3+3" model, with a dose ascent starting from 120mg qd
|
| Experimental: BEBT-109 180mg BEBT-109 orally at an initial dose of 180 mg once daily. |
Drug: BEBT-109
BEBT-109 is based on the "3+3" model, with a dose ascent starting from 120mg qd
|
| Experimental: BEBT-109 240mg BEBT-109 orally at an initial dose of 240mg (120mg bid) once daily. |
Drug: BEBT-109
BEBT-109 is based on the "3+3" model, with a dose ascent starting from 120mg qd
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Sign written informed consent before implementing any trial-related procedures;
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Age ≥18 years and no limit on the gender.
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Histologically or cytologically confirmed locally advanced or metastatic NSCLC with EGFR exon20ins mutation according to assessments made in local laboratories.
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Previous treatment and type of mutation:
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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.
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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.
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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).
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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.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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Patients with brain metastasis were only enrolled if the metastases were stable.
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Subjects had at least 1 measurable lesion that met the RECIST 1.1 criteria.
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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:
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Combined with any other malignancy (except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix).
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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.
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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.
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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.
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Those who have not withdrawn from other clinical trials within 4 weeks prior to the first administration of the study treatment.
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Previous homogeneous drug restriction:
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Patients with EGFR mutation previously treated with osimertinib or other third-generation EGFR inhibitor drugs (eg, ivelitinib, emetinib, and eflotinib) ;
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EGFR exon20 insertion mutants have used drugs that target EGFR 20 exon insertion mutants (e.g. Poziotinib tarloxotinib TAK788 JNJ-61186372 CLN-081, etc.)
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Other EGFR rare mutations (EGFR G719A, L861Q, or S768I point mutations) have been treated with afatinib.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hunan Cancer hospital | Changsha | Hunan | China |
Sponsors and Collaborators
- Hunan Province Tumor Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BEBT-109