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

A Phase 1/2, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of BBT-176 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Who Progressed Following Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Agent

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).

Study Overview

• Status: Terminated
• Conditions: NSCLC
• Intervention / Treatment: Drug: BBT-176, QD; Drug: BBT-176, BID

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13605
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 20mg QD; BBT-176: 20mg, Orally, Once daily (QD)	Drug: BBT-176, QD; BBT-176 given orally alone, QD
Experimental: 80mg QD; BBT-176: 80mg, Orally, QD	Drug: BBT-176, QD; BBT-176 given orally alone, QD
Experimental: 160mg QD; BBT-176: 160mg, Orally, QD	Drug: BBT-176, QD; BBT-176 given orally alone, QD
Experimental: 320mg QD; BBT-176: 320mg, Orally, QD	Drug: BBT-176, QD; BBT-176 given orally alone, QD
Experimental: 480mg QD; BBT-176: 480mg, Orally, QD	Drug: BBT-176, QD; BBT-176 given orally alone, QD
Experimental: 600mg QD; BBT-176: 600mg, Orally, QD	Drug: BBT-176, QD; BBT-176 given orally alone, QD
Experimental: 160mg, BID; BBT-176: 160mg, Orally, Twice daily (BID)	Drug: BBT-176, BID; BBT-176 given orally alone, BID
Experimental: 200mg, BID; BBT-176: 200mg, Orally, BID	Drug: BBT-176, BID; BBT-176 given orally alone, BID
Experimental: 240mg, BID; BBT-176: 240mg, Orally, BID	Drug: BBT-176, BID; BBT-176 given orally alone, BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part 2) Objective Response Rate (ORR)	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.	Every 6 weeks
(Part 1) Incidence of Adverse Events and Clinical Laboratory Abnormalities Defined as Dose-limiting Toxicities (DLTs)	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.	21 days from the first dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Part 1) Objective Response Rate (ORR)	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.	Every 6 weeks, approximately 1 year
(Part 2) Duration of Response (DoR)	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.	throughout study completion, approximately 1 year
(Part 2) Progression Free Survival (PFS)	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.	throughout study completion, approximately 1 year
(Part 1) Pharmacokinetics (PK) Parameters - Peak Concentration (Cmax)	Peak plasma concentration (Cmax) of BBT-176 from Part 1.	0, 1, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 1 (C1D1) and Cycle 2 Day 1 (C2D1) (each cycle is 21 days)
(Part 1) PK Parameters - Area Under the Concentration-time Curve (AUC)	Area under the plasma concentration-time curve (AUC) of BBT-176 from Part 1.	0, 1, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 1 (C1D1) and Cycle 2 Day 1 (C2D1) (each cycle is 21 days)
(Part 2) Incidence of Adverse Event (AE)s	Number of patients experiencing adverse event (AE)s	throughout study completion, approximately 1 year
(Part 2) BBT-176 Concentrations	Plasma BBT-176 concentrations at steady state	At Cycle 2 Day 1 (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Bridge Biotherapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2021
• Primary Completion (Actual): November 29, 2023
• Study Completion (Actual): November 29, 2023

Study Registration Dates

• First Submitted: March 23, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: BBT176-ONC-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No