Phase 1/2 Study of BBT-176 in Advanced NSCLC With Progression After EGFR TKI Treatment

Phase 1

Terminated

• Conditions: NSCLC
• Interventions: Drug: BBT-176

• Registration Number: NCT04820023
• Lead Sponsor: Bridge Biotherapeutics, Inc.

Brief Summary

This clinical trial is the first-in-human study of BBT-176. The purpose of this trial is to investigate the safety and tolerability of BBT-176 (Part 1) and to evaluate the anti-tumor activity of BBT-176 (Part 2).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-03-23
• Study First Submitted QC: 2021-03-25
• Study First Posted: 2021-03-29
• Study Start: 2021-04-02
• Primary Completion: 2023-11-29
• Study Completion: 2023-11-29
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-12
• Last Update Posted: 2023-12-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Provision of signed and dated, written informed consent before any study specific procedures, sampling and analyses

• Histological or cytological confirmation of advanced and/or metastatic stage IIIB/IV NSCLC

• Radiological documentation of disease progression while on a previous continuous (at least 30 days) treatment with an EGFR TKI monotherapy (including, but not limited to, osimertinib, afatinib, gefitinib, or erlotinib)

• Patients must fulfill one of the following:

  • Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including, but not limited to, exon 19 deletion, L858R, or L861Q)
  • Documented partial or complete response or a significant and durable stable disease (at least 6 months), based on the RECIST or WHO criteria, after treatment of an EGFR TKI

Key

Exclusion Criteria

• Treatment with any of the following:

  • An EGFR TKI, including but not limited to osimertinib, afatinib, gefitinib, or erlotinib within 8 days of the first dose of study treatment.
  • Any cytotoxic chemotherapy, investigational agents, or anticancer drugs for the treatment of advanced NSCLC, between prior EGFR TKI treatment and BBT-176 treatment
  • Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
  • Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment
  • Patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation within 6 weeks of the first dose of study treatment

• Any unresolved toxicities from prior therapy greater than NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2 neuropathy related to prior platinum-therapy

• Spinal cord compression or brain metastases, unless asymptomatic and stable

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BBT-176	BBT-176	-

Primary Outcome Measures

Name	Time	Method
(Part 2) Objective Response Rate (ORR)	Every 6 weeks	ORR is estimated by the number of patients with a best overall response of CR or PR divided by the total number of patients who are evaluable for efficacy.
(Part 1) Incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs)	21 days from the first dosing	any toxicity not attributable to the disease or disease-related processes under investigation that occurs from the first dose of study treatment in dose-escalation cohorts as defined in the protocol.

Secondary Outcome Measures

Name	Time	Method
(Part 1) PK parameters - area under the concentration-time curve (AUC)	Up to Cycle 2 Day 1 (each cycle is 21 days)	Area under the plasma concentration-time curve of BBT-176
(Part 1) Objective Response Rate (ORR)	Every 6 weeks, approximately 1 year	ORR is estimated by the number of patients with a best overall response of Complete Response (CR) or Partial Response (PR) divided by the total number of patients who are evaluable for efficacy.
(Part 1) PK parameters - peak concentration (Cmax)	Up to Cycle 2 Day 1 (each cycle is 21 days)	Peak plasma concentration of BBT-176
(Part 2) Incidence of Adverse Event (AE)s	throughout study completion, approximately 1 year	Number of patients experiencing AEs
(Part 2) BBT-176 concentrations	At Cycle 2 Day 1 (each cycle is 21 days)	Plasma BBT-176 concentrations at steady state
(Part 2) Progression Free Survival (PFS)	throughout study completion, approximately 1 year	PFS will be calculated for each patient as the number of days from the first day of treatment to the date of the first documented disease progression or date of death, whichever occurs first.
(Part 2) Duration of Response (DoR)	throughout study completion, approximately 1 year	DoR is calculated for every patient with a response to therapy (PR and CR) and is defined as the number of days from the date of initial response to the date of the first documented disease progression/relapse (including clinical progression) or death, whichever occurs first.

Trial Locations

Locations (4)

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Gyeonggi-do, Korea, Republic of

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of