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

NCT06001671 | Completed Phase 1

• 1 other identifier: BEBT-109
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (2)

• DLT

  Defined as one of adverse events defined by NCI CTCAE V5.0 from the first day to the 28th day of the treatment period.

  2 years

• MTD

  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).

  2 years

Secondary Outcomes (2)

• ORR

  2 years

• DCR

  2 years

Study Arms (3)

BEBT-109 120mg

EXPERIMENTAL

BEBT-109 orally at an initial dose of 120 mg once daily.

Drug: BEBT-109

BEBT-109 180mg

EXPERIMENTAL

BEBT-109 orally at an initial dose of 180 mg once daily.

Drug: BEBT-109

BEBT-109 240mg

EXPERIMENTAL

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

Drug: BEBT-109

Interventions

BEBT-109 DRUG

BEBT-109 is based on the "3+3" model, with a dose ascent starting from 120mg qd

BEBT-109 120mg; BEBT-109 180mg; BEBT-109 240mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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.
• 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).
• 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.

You may not qualify if:

• 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.
• 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:
• Patients with EGFR mutation previously treated with osimertinib or other third-generation EGFR inhibitor drugs (eg, ivelitinib, emetinib, and eflotinib) ;
• EGFR exon20 insertion mutants have used drugs that target EGFR 20 exon insertion mutants (e.g. Poziotinib tarloxotinib TAK788 JNJ-61186372 CLN-081, etc.)
• Other EGFR rare mutations (EGFR G719A, L861Q, or S768I point mutations) have been treated with afatinib.

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (1)

Hunan Cancer hospital

Changsha, Hunan, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Deputy Director of Thoracic Oncology Department

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: August 21, 2023
• Study Start: October 27, 2020
• Primary Completion: March 1, 2023
• Study Completion: August 8, 2023
• Last Updated: October 6, 2023

Record last verified: 2023-10

Locations

CN (1)