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

NCT04820023 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: BBT176-ONC-001
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 4

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).

Conditions

NSCLC

Outcome Measures

Primary Outcomes (2)

• (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

• (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

Secondary Outcomes (7)

• (Part 1) Objective Response Rate (ORR)

  Every 6 weeks, approximately 1 year

• (Part 1) Pharmacokinetics (PK) Parameters - Peak Concentration (Cmax)

  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)

  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) Duration of Response (DoR)

  throughout study completion, approximately 1 year

• (Part 2) Incidence of Adverse Event (AE)s

  throughout study completion, approximately 1 year

Study Arms (9)

20mg QD

EXPERIMENTAL

BBT-176: 20mg, Orally, Once daily (QD)

Drug: BBT-176, QD

80mg QD

EXPERIMENTAL

BBT-176: 80mg, Orally, QD

Drug: BBT-176, QD

160mg QD

EXPERIMENTAL

BBT-176: 160mg, Orally, QD

Drug: BBT-176, QD

320mg QD

EXPERIMENTAL

BBT-176: 320mg, Orally, QD

Drug: BBT-176, QD

480mg QD

EXPERIMENTAL

BBT-176: 480mg, Orally, QD

Drug: BBT-176, QD

600mg QD

EXPERIMENTAL

BBT-176: 600mg, Orally, QD

Drug: BBT-176, QD

160mg, BID

EXPERIMENTAL

BBT-176: 160mg, Orally, Twice daily (BID)

Drug: BBT-176, BID

200mg, BID

EXPERIMENTAL

BBT-176: 200mg, Orally, BID

Drug: BBT-176, BID

240mg, BID

EXPERIMENTAL

BBT-176: 240mg, Orally, BID

Drug: BBT-176, BID

Interventions

BBT-176, QD DRUG

BBT-176 given orally alone, QD

160mg QD; 20mg QD; 320mg QD; 480mg QD; 600mg QD; 80mg QD

BBT-176, BID DRUG

BBT-176 given orally alone, BID

160mg, BID; 200mg, BID; 240mg, BID

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bridge Biotherapeutics, Inc.: lead

Study Sites (4)

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13605, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

Related Publications (1)

• Lim SM, Fujino T, Kim C, Lee G, Lee YH, Kim DW, Ahn JS, Mitsudomi T, Jin T, Lee SY. BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non-Small Cell Lung Cancer. Clin Cancer Res. 2023 Aug 15;29(16):3004-3016. doi: 10.1158/1078-0432.CCR-22-3901.

  PMID: 37249619 DERIVED

MeSH Terms

Interventions

BID protein, human

Limitations and Caveats

The study was terminated early during Part 1, and Part 2 (Phase 2) was not initiated, resulting in no data available for analysis.

Results Point of Contact

• Title: Clinical Trial Lead
• Organization: Bridge Biotherapeutics, Inc.

Clinicaltrials.gov_inquiries@bridgebiorx.com

+82-31-8092-3280

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2021
• First Posted: March 29, 2021
• Study Start: April 2, 2021
• Primary Completion: November 29, 2023
• Study Completion: November 29, 2023
• Last Updated: June 6, 2025
• Results First Posted: June 6, 2025

Record last verified: 2025-06

Locations

KR (4)