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Sponsor's decision considering the changing treatment landscape for NSCLC
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 20mg QD | Experimental | BBT-176: 20mg, Orally, Once daily (QD) |
|
| 80mg QD | Experimental | BBT-176: 80mg, Orally, QD |
|
| 160mg QD | Experimental | BBT-176: 160mg, Orally, QD |
|
| 320mg QD | Experimental | BBT-176: 320mg, Orally, QD |
|
| 480mg QD | Experimental | BBT-176: 480mg, Orally, QD |
|
| 600mg QD | Experimental | BBT-176: 600mg, Orally, QD |
|
| 160mg, BID |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BBT-176, QD | Drug | BBT-176 given orally alone, QD |
|
| Measure | Description | Time Frame |
|---|---|---|
| (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 |
| 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 1) Pharmacokinetics (PK) Parameters - Peak Concentration (Cmax) |
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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:
Key Exclusion Criteria:
Treatment with any of the following:
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
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seoul National University Bundang Hospital | Seongnam-si | Gyeonggi-do | 13605 | South Korea | ||
| Samsung Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37249619 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 20mg QD | BBT-176: 20mg, Orally, QD |
| FG001 | 80mg QD | BBT-176: 80mg, Orally, QD |
| FG002 | 160mg, QD | BBT-176: 160mg, Orally, QD |
| FG003 | 320mg, QD | BBT-176: 320mg, Orally, QD |
| FG004 | 480mg, QD | BBT-176: 480mg, Orally, QD |
| FG005 | 600mg, QD | BBT-176: 600mg, Orally, QD |
| FG006 | 160mg, BID | BBT-176: 160mg, Orally, BID |
| FG007 | 200mg, BID | BBT-176: 200mg, Orally, BID |
| FG008 | 240mg, BID | BBT-176: 240mg, Orally, BID |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Each treatment cycle is 21 days.
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| ID | Title | Description |
|---|---|---|
| BG000 | 20mg QD | BBT-176: 20mg, Orally, QD |
| BG001 | 80mg QD | BBT-176: 80mg, Orally, QD |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | (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. | Posted | Count of Participants | Participants | 21 days from the first dosing |
|
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.
Due to early termination of the study, analysis was not conducted.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 20mg QD | BBT-176: 20mg, QD, Orally | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastritis | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
The study was terminated early during Part 1, and Part 2 (Phase 2) was not initiated, resulting in no data available for analysis.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Lead | Bridge Biotherapeutics, Inc. | +82-31-8092-3280 | Clinicaltrials.gov_inquiries@bridgebiorx.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 26, 2022 | Jan 6, 2025 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 28, 2021 | Jan 6, 2025 | SAP_003.pdf |
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| ID | Term |
|---|---|
| C494814 | BID protein, human |
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| Experimental |
BBT-176: 160mg, Orally, Twice daily (BID) |
|
| 200mg, BID | Experimental | BBT-176: 200mg, Orally, BID |
|
| 240mg, BID | Experimental | BBT-176: 240mg, Orally, BID |
|
| BBT-176, BID | Drug | BBT-176 given orally alone, BID |
|
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) 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) 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) |
| (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 |
| Seoul |
| South Korea |
| Seoul National University Hospital | Seoul | South Korea |
| Severance Hospital | Seoul | South Korea |
| Withdrawal by Subject |
|
| Progressive Disease |
|
| New anti-cancer therapy |
|
| Other |
|
| BG002 |
| 160mg QD |
BBT-176: 160mg, Orally, QD |
| BG003 | 320mg QD | BBT-176: 320mg, Orally, QD |
| BG004 | 480mg QD | BBT-176: 480mg, Orally, QD |
| BG005 | 600mg QD | BBT-176: 600mg, Orally, QD |
| BG006 | 160mg BID | BBT-176: 160mg, Orally, BID |
| BG007 | 200mg BID | BBT-176: 200mg, Orally, BID |
| BG008 | 240mg BID | BBT-176: 240mg, Orally, BID |
| BG009 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
BBT-176: 160mg, Orally, QD |
| OG003 | 320mg, QD | BBT-176: 320mg, Orally, QD |
| OG004 | 480mg, QD | BBT-176: 480mg, Orally, QD |
| OG005 | 600mg, QD | BBT-176: 600mg, Orally, QD |
| OG006 | 160mg, BID | BBT-176: 160mg, Orally, BID |
| OG007 | 200mg, BID | BBT-176: 200mg, Orally, BID |
| OG008 | 240mg, BID | BBT-176: 240mg, Orally, BID |
|
|
| Primary | (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. | Due to early termination of the study, Part 2 and analysis was not conducted. | Posted | Every 6 weeks |
|
|
| Secondary | (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. | Posted | Count of Participants | Participants | Every 6 weeks, approximately 1 year |
|
|
|
| Secondary | (Part 1) Pharmacokinetics (PK) Parameters - Peak Concentration (Cmax) | Peak plasma concentration (Cmax) of BBT-176 from Part 1. | The presentation of PK data on C1D1 and C2D1 was due to that the PK samples were collected on those dates. PK samples were collected at 600 mg QD, but drug exposure was low due to vomiting, making it impossible to determine PK parameters. | Posted | Mean | Standard Deviation | ng/mL | 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) |
|
|
|
| Secondary | (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. | PK data were presented on C1D1 and C2D1 as samples were collected on those days. In the BID regimen, AUC 0-12 was calculated on both days. AUC 0-24 was estimated on C2D1 using AUC 0-12, assuming steady state, but not on C1D1 since steady state was not reached. In Cohort 6 (600mg QD), PK parameters were not determined as BBT-176 was not tolerable, and drug exposure was low due to vomiting. | Posted | Mean | Standard Deviation | ng*hr/mL | 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) |
|
|
|
| Secondary | (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. | Due to early termination of the study, Part 2 and analysis was not conducted. | Posted | throughout study completion, approximately 1 year |
|
|
| Secondary | (Part 2) Incidence of Adverse Event (AE)s | Number of patients experiencing adverse event (AE)s | Due to early termination of the study, Part 2 and analysis was not conducted. | Posted | throughout study completion, approximately 1 year |
|
|
| Secondary | (Part 2) BBT-176 Concentrations | Plasma BBT-176 concentrations at steady state | Due to early termination of the study, Part 2 and analysis was not conducted. | Posted | At Cycle 2 Day 1 (each cycle is 21 days) |
|
|
| Secondary | (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. | Due to early termination of the study, Part 2 and analysis was not conducted. | Posted | throughout study completion, approximately 1 year |
|
|
| 4 |
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | 80mg QD | BBT-176: 80mg, QD, Orally | 0 | 3 | 0 | 3 | 2 | 3 |
| EG002 | 160mg QD | BBT-176: 160mg, QD, Orally | 0 | 4 | 2 | 4 | 3 | 4 |
| EG003 | 320mg QD | BBT-176: 320mg, QD, Orally | 0 | 3 | 1 | 3 | 3 | 3 |
| EG004 | 480mg QD | BBT-176: 480mg, QD, Orally | 0 | 8 | 4 | 8 | 8 | 8 |
| EG005 | 600mg QD | BBT-176: 600mg, QD, Orally | 0 | 3 | 1 | 3 | 3 | 3 |
| EG006 | 160mg BID | BBT-176: 160mg, BID, Orally | 1 | 5 | 3 | 5 | 4 | 5 |
| EG007 | 200mg BID | BBT-176: 200mg, BID, Orally | 0 | 9 | 6 | 9 | 9 | 9 |
| EG008 | 240mg BID | BBT-176: 240mg, BID, Orally | 1 | 6 | 6 | 6 | 6 | 6 |
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pneumonia | Infections and infestations | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | Systematic Assessment |
|
| Pneumonia | Infections and infestations | Systematic Assessment |
|
| COVID-19 related Pneumonia | Infections and infestations | Systematic Assessment |
|
| Sepsis | Infections and infestations | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Sudden death | General disorders | Systematic Assessment |
|
| Hypotension | Vascular disorders | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| Drug eruption | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hand dermatitis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pelvic fracture | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Seizure | Nervous system disorders | Systematic Assessment |
|
| Skin abrasion | Nervous system disorders | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Amylase Increased | Investigations | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
|
| Gastric ulcer | Gastrointestinal disorders | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Drug eruption | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hand dermatitis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
|
| Blood pressure increased | Investigations | Systematic Assessment |
|
| Lipase increased | Investigations | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
| Weight decreased | Investigations | Systematic Assessment |
|
| Blood creatinine increased | Investigations | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| COVID-19 infection | Infections and infestations | Systematic Assessment |
|
| Pneumonia | Infections and infestations | Systematic Assessment |
|
| Influenza | Infections and infestations | Systematic Assessment |
|
| Atrial tachycardia | Cardiac disorders | Systematic Assessment |
|
| Vision blurred | Eye disorders | Systematic Assessment |
|
| Eczema eyelids | Eye disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Face oedema | General disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Swelling face | General disorders | Systematic Assessment |
|
| Asthenia | General disorders | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
|
| Glucose tolerance impaired | Metabolism and nutrition disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dyspnea exertional | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Delirium | Psychiatric disorders | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Pelvic fracture | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | Systematic Assessment |
|
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