Antitumor Activity and Safety of BEBT-109, a Novel EGFR Inhibitor, in Previously Treated NSCLC

Phase 1

Completed

• Conditions: NSCLC
• Interventions: Drug: BEBT-109

• Registration Number: NCT06001671
• Lead Sponsor: Hunan Province Tumor Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-10-27
• Primary Completion: 2023-03-01
• Study First Submitted: 2023-08-07
• Study Completion: 2023-08-08
• Study First Submitted QC: 2023-08-14
• Study First Posted: 2023-08-21
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-05
• Last Update Posted: 2023-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BEBT-109 120mg	BEBT-109	BEBT-109 orally at an initial dose of 120 mg once daily.
BEBT-109 240mg	BEBT-109	BEBT-109 orally at an initial dose of 240mg (120mg bid) once daily.
BEBT-109 180mg	BEBT-109	BEBT-109 orally at an initial dose of 180 mg once daily.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
DCR	2 years	Defined as the proportion of subjects with complete remission (CR), partial remission (PR) and stable disease (SD) to the total subjects
ORR	2 years	Defined as the proportion of subjects in complete remission (CR) and partial remission (PR) to the total subjects

Trial Locations

Locations (1)

Hunan Cancer hospital; 🇨🇳 Changsha, Hunan, China