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NCT04820023

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

Terminated Phase 1, PHASE2 Results posted Last updated 6 June 2025
What this trial tests

Phase 1, PHASE2 trial testing BBT-176, QD in NSCLC in 45 participants. Terminated before completion.

Timeline
2 April 2021
Primary endpoint
29 November 2023
29 November 2023

Quick facts

Lead sponsorBridge Biotherapeutics, Inc.
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment45
Start date2 April 2021
Primary completion29 November 2023
Estimated completion29 November 2023
Sites4 locations across South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Bridge Biotherapeutics, Inc. — full company profile →

Who can join

18 and older, any sex, with NSCLC. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

(Part 1) Incidence of Adverse Events and Clinical Laboratory Abnormalities Defined as Dose-limiting Toxicities (DLTs) Primary · 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.

GroupValue95% CI
20mg QD0
80mg QD0
160mg, QD0
320mg, QD0
480mg, QD0
600mg, QD0
160mg, BID0
200mg, BID1
240mg, BID1
(Part 1) Objective Response Rate (ORR) Secondary · 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.

GroupValue95% CI
20mg QD0
80mg QD0
160mg, QD1
320mg, QD0
480mg, QD0
600mg, QD0
160mg, BID0
200mg, BID0
240mg, BID1
(Part 1) Pharmacokinetics (PK) Parameters - Peak Concentration (Cmax) Secondary · 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)

Peak plasma concentration (Cmax) of BBT-176 from Part 1.

GroupValue95% CI
20mg QD C1D17± 4
20mg QD C2D110± 5
80mg QD C1D1159± 67
80mg QD C2D1260± 37
160mg QD C1D1240± 75
160mg QD C2D1638± 231
320mg QD C1D1594± 94
320mg QD C2D11416± 370
480mg QD C1D11087± 470
480mg QD C2D12145± 1438
600mg QD C1D1NA± NA
600mg QD C2D1NA± NA
(Part 1) PK Parameters - Area Under the Concentration-time Curve (AUC) Secondary · 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)

Area under the plasma concentration-time curve (AUC) of BBT-176 from Part 1.

GroupValue95% CI
20mg QD C1D191± 42
20mg QD C2D1192± 89
80mg QD C1D11314± 263
80mg QD C2D13584± 158
160mg QD C1D12799± 1030
160mg QD C2D19652± 5978
320mg QD C1D18065± 2703
320mg QD C2D121992± 5494
480mg QD C1D113938± 6315
480mg QD C2D138365± 21815
600mg QD C1D1NA± NA
600mg QD C2D1NA± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Safety monitoring was performed up to 30 days (± 3 days) after the last administration of study drug or immediately before initiation of any other cancer therapies, an average of 6 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

20mg QD
Serious: 0/4 (0%)
Deaths: 0/4
80mg QD
Serious: 0/3 (0%)
Deaths: 0/3
160mg QD
Serious: 2/4 (50%)
Deaths: 0/4
320mg QD
Serious: 1/3 (33%)
Deaths: 0/3
480mg QD
Serious: 4/8 (50%)
Deaths: 0/8
600mg QD
Serious: 1/3 (33%)
Deaths: 0/3
160mg BID
Serious: 3/5 (60%)
Deaths: 1/5
200mg BID
Serious: 6/9 (67%)
Deaths: 0/9
240mg BID
Serious: 6/6 (100%)
Deaths: 1/6

Serious adverse events (26 terms)

ReactionSystem20mg QD80mg QD160mg QD320mg QD480mg QD600mg QD160mg BID200mg BID240mg BID
PneumoniaInfections and infestations
PneumoniaInfections and infestations
GastritisGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
StomatitisGastrointestinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Pericardial effusionCardiac disorders
COVID-19 related PneumoniaInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
PyrexiaGeneral disorders
Sudden deathGeneral disorders
HypotensionVascular disorders
Neutrophil count decreasedInvestigations
Drug eruptionSkin and subcutaneous tissue disorders
Hand dermatitisSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
AnemiaBlood and lymphatic system disorders
Pelvic fractureInjury, poisoning and procedural complications
SeizureNervous system disorders
Skin abrasionNervous system disorders
Other adverse events (73 terms — click to expand)

ReactionSystem20mg QD80mg QD160mg QD320mg QD480mg QD600mg QD160mg BID200mg BID240mg BID
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
StomatitisGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
AnemiaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
Urinary tract infectionInfections and infestations
PyrexiaGeneral disorders
HaematuriaRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
Amylase IncreasedInvestigations
GastritisGastrointestinal disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
CheilitisGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Gastric ulcerGastrointestinal disorders
DysphagiaGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
Dermatitis acneiformSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
ErythemaSkin and subcutaneous tissue disorders
Drug eruptionSkin and subcutaneous tissue disorders
EczemaSkin and subcutaneous tissue disorders
Hand dermatitisSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
Blood pressure increasedInvestigations
Lipase increasedInvestigations
Neutrophil count decreasedInvestigations
Weight decreasedInvestigations
Blood creatinine increasedInvestigations
Hepatic enzyme increasedInvestigations

Most-reported serious reactions: Pneumonia, Pneumonia, Gastritis, Diarrhoea, Nausea, Stomatitis, Pleural effusion, Pneumonitis.

Data from ClinicalTrials.gov NCT04820023 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer.
    To C, Beyett TS, Jang J, Feng WW, et al · · 2022 · cited 104× · PMID 35422503 · DOI 10.1038/s43018-022-00351-8
  2. Structural Insight and Development of EGFR Tyrosine Kinase Inhibitors.
    Amelia T, Kartasasmita RE, Ohwada T, Tjahjono DH. · · 2022 · cited 83× · PMID 35164092 · DOI 10.3390/molecules27030819
  3. Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer.
    Chhouri H, Alexandre D, Grumolato L. · · 2023 · cited 67× · PMID 36672453 · DOI 10.3390/cancers15020504
  4. Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance.
    Araki T, Kanda S, Horinouchi H, Ohe Y. · · 2023 · cited 59× · PMID 37279591 · DOI 10.1093/jjco/hyad052
  5. BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non-Small Cell Lung Cancer.
    Lim SM, Fujino T, Kim C, Lee G, et al · · 2023 · cited 57× · PMID 37249619 · DOI 10.1158/1078-0432.ccr-22-3901
  6. Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer.
    You KS, Yi YW, Cho J, Park JS, et al · · 2021 · cited 48× · PMID 34207383 · DOI 10.3390/ph14060589
  7. Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer.
    Li S, de Camargo Correia GS, Wang J, Manochakian R, et al · · 2023 · cited 47× · PMID 37296863 · DOI 10.3390/cancers15112899
  8. The Right Partner in Crime: Unlocking the Potential of the Anti-EGFR Antibody Cetuximab <i>via</i> Combination With Natural Killer Cell Chartering Immunotherapeutic Strategies.
    Baysal H, De Pauw I, Zaryouh H, Peeters M, et al · · 2021 · cited 41× · PMID 34557197 · DOI 10.3389/fimmu.2021.737311

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04820023.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing