A Study of BGB324 (Bemcentinib) in Combination With Erlotinib in Patients With Non-Small Cell Lung Cancer
NCT ID: NCT02424617
Last Updated: 2025-02-26
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1/PHASE2
40 participants
INTERVENTIONAL
2015-04-19
2021-08-25
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
NCT03184571
Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Followed by Radiation Therapy and Erlotinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00553462
A Study Comparing Bevacizumab Therapy With or Without Erlotinib for First-Line Treatment of Non-Small Cell Lung Cancer (ATLAS)
NCT00257608
A Study to Evaluate the Efficacy and Safety of Serplulimab in Combination With Chemotherapy and Concurrent Radiotherapy in Patients With Limited-Stage Small Cell Lung Cancer
NCT05353257
Safety, Efficacy, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer
NCT06712316
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Total 40 participants with histologically- or cytologically-confirmed Stage IIIb or Stage IV NSCLC received bemcentinib (BGB324) as a single agent (Run-in Cohort) or in combination with erlotinib (Arms A, B, and C).
Run-in Arm to establish the safety and tolerability of bemcentinib (BGB324) administered as a single agent; bemcentinib was administered at a loading dose of 600 mg on Day 1 and Day 2 of Cycle 1, followed by 200 mg daily thereafter. After 6 participants have been dosed and safety established; Arm A (dose escalation arm) was opened to confirm the bemcentinib dose to be used in combination with erlotinib.
In Arm A the dose of bemcentinib (BGB324) was escalated in a standard 3+3 fashion until a maximum tolerated dose (MTD) of the combination (bemcentinib + erlotinib) was established. The dose of bemcentinib to be investigated in Arm B and C was confirmed upon recommendation of a Safety Review Committee.
Arm B and C was open in parallel to investigate bemcentinib in combination with erlotinib.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Phase 1- Run in Arm (Bemcentinib Monotherapy)
Participants in this arm received bemcentinib as monotherapy. This was to determine the safety and tolerability of bemcentinib when administered alone.
Bemcentinib
Participants received bemcentinib 600 mg on Days 1 and 2 as loading dose and bemcentinib 200 mg as daily maintenance dose for the 21-day cycle.
Phase 1- Arm A (Bemcentinib + Erlotinib)
Participants in this arm received erlotinib with bemcentinib. A standard 3+3 design to determine the dose of bemcentinib that could be safely administered in combination with erlotinib in participants who had received prior treatment with erlotinib. This was to determine the maximum tolerated dose of bemcentinib that could be safely administered with erlotinib.
Erlotinib
Participants received erlotinib 150 mg for the 21-day cycle.
Bemcentinib
Participants received starting loading dose of bemcentinib 600 mg (200 mg on Days 1, 2 and 3) and bemcentinib 100 mg as daily maintenance dose for the 21-day cycle.
Depending on tolerability and DLT, the loading dose of bemcentinib was escalated to 800mg (400 mg on Days 1 and 2) and bemcentinib 100 mg as daily maintenance for the 21- day cycle and to 1200 mg daily (600 mg on Days 1 and 2, or 400 mg on Days 1, 2 and 3) and bemcentinib 200 mg as daily maintenance for the 21- day cycle).
Phase 2- Arm B (Bemcentinib + Erlotinib)
Participants in this arm received erlotinib with bemcentinib in participants with an activating epidermal growth factor receptor (EGFR) mutation who are T790M negative and who had progressed after receiving treatment with an approved EGFR tyrosine kinase inhibitor (TKI) \[osimertinib, afatinib, or gefitinib\].
Erlotinib
Participants received erlotinib 150 mg for the 21-day cycle.
Bemcentinib
Participants received bemcentinib 400 mg on Days 1, 2 and 3 as loading dose and bemcentinib 200 mg as daily maintenance dose for the 21-day cycle.
Phase 2- Arm C (Bemcentinib + Erlotinib)
Participants in this arm received erlotinib daily along with bemcentinib in participants with an activating EGFR mutation (including exon 19 deletion or exon 21 \[L858R\] substitution or other rearrangement of the EGFR gene mutation) who had received greater than or equal to (≥) 12 weeks of erlotinib without disease progression.
Erlotinib
Participants received erlotinib 150 mg for the 21-day cycle.
Bemcentinib
Participants received bemcentinib 400 mg on Days 1, 2 and 3 as loading dose and bemcentinib 200 mg as daily maintenance dose for the 21-day cycle.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Erlotinib
Participants received erlotinib 150 mg for the 21-day cycle.
Bemcentinib
Participants received bemcentinib 600 mg on Days 1 and 2 as loading dose and bemcentinib 200 mg as daily maintenance dose for the 21-day cycle.
Bemcentinib
Participants received starting loading dose of bemcentinib 600 mg (200 mg on Days 1, 2 and 3) and bemcentinib 100 mg as daily maintenance dose for the 21-day cycle.
Depending on tolerability and DLT, the loading dose of bemcentinib was escalated to 800mg (400 mg on Days 1 and 2) and bemcentinib 100 mg as daily maintenance for the 21- day cycle and to 1200 mg daily (600 mg on Days 1 and 2, or 400 mg on Days 1, 2 and 3) and bemcentinib 200 mg as daily maintenance for the 21- day cycle).
Bemcentinib
Participants received bemcentinib 400 mg on Days 1, 2 and 3 as loading dose and bemcentinib 200 mg as daily maintenance dose for the 21-day cycle.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
7. Has exhausted existing licensed therapies, or is unsuitable for treatment with existing licensed therapies for NSCLC.
8. Known EGFR mutation status.
9. Either:
1. Has received ≥ 6 weeks historical treatment with erlotinib. Erlotinib treatment must be re started ≥ 1 week before the first dose of bemcentinib (Cycle 1, Day 1).
Or:
2. Is currently receiving erlotinib treatment for NSCLC and will have received ≥ 6 weeks treatment at the time of the first dose of bemcentinib (Cycle 1, Day 1).
10. Erlotinib-related toxicities being well-controlled and \<Grade 3 in severity at the time of the first dose of bemcentinib (Cycle 1, Day 1).
11. Toxicity from other prior therapy has resolved to ≤ Grade 1 (previous treatment with bevacizumab and other licensed antibody therapies is permitted).
12. Participants must have documented EGFR mutation (including exon 19 deletion or exon 21 L85R substitution or other rearrangement of the EGFR gene). EGFR mutation may be confirmed historically (prior to study entry) and during the 28 day screening period confirmation of negative T790M status (confirmed with blood test or biopsy from a progressing tumor). Participants who have previously been treated with a T790M inhibitor (i.e., osimertinib) and have progressed will not require T790M testing (the 28-day screening period could be extended to allow for confirmation of the T790M status. Other assessments including computed tomography were conducted in the 28-day screening period).
13. Disease that is measurable according to the response evaluation criteria in solid tumors (RECIST) Version 1.1.
14. Has progressed after receiving erlotinib or any other an approved EGFR inhibitor (i.e., afatinib, or gefitinib) at any time during therapy for advanced disease.
15. Erlotinib related toxicities being well-controlled and \<Grade 3 in severity at the time of the first dose of bemcentinib (Cycle 1, Day 1). Toxicities associated with other EGFR inhibitors to be \<Grade 2 in severity at the time of first dose of bemcentinib.
16. Participants must have completed afatinib and/or gefitinib treatment at least 1 week before the first dose of bemcentinib.
17. Toxicity from other prior therapy has resolved to ≤ Grade 1 (previous treatment with bevacizumab and other licensed antibody therapies is permitted).
18. Participants who have an activating EGFR mutation may have up to 4 lines of previous treatment in the advanced setting. Additional chemotherapy may also have been given for treatment of limited stage disease in the adjuvant setting provided this was completed at least 6 months prior to study treatment.
19. Known EGFR mutation status:
20. Presence of an activating EGFR mutation (including exon 19 deletion or exon 21 \[L858R\] substitution mutation or other rearrangement of the EGFR gene).
21. Disease that is measurable or evaluable according to RECIST Version 1.1.
22. Is currently receiving erlotinib for NSCLC and will have received ≥12 weeks' treatment at the time of the first dose of bemcentinib (Cycle 1, Day 1).
23. Have erlotinib-related toxicities that are well controlled and \<Grade 3 in severity the time of the first dose of bemcentinib (Cycle 1, Day 1).
24. No prior treatment for advanced NSCLC except erlotinib and/or previous surgery (participants who have received treatment for their NSCLC while awaiting confirmation of EGFR status, may be eligible to participate and the inclusion of such participants should be discussed with the Medical Monitor).
Exclusion Criteria
2. Abnormal left ventricular ejection fraction (less than the lower limit of normal for a participants of that age at the treating institution or \<45%).
3. Treatment with any of the following; histamine receptor 2 inhibitors, proton pump inhibitors or antacids within 3 days or 5 half-lives, whichever is longer. The Investigator may initiate rescue treatment with these medications during the study, providing they are taken in the evening.
4. History of an ischemic cardiac event, including myocardial infarction, within 3 months of consent.
5. Pulmonary hemorrhage or hemoptysis \>2.5 mL blood within 6 weeks of consent unless cause has been addressed and is medically resolved.
6. Congestive cardiac failure of \>Class II severity according to the New York Heart Association (NYHA) defined as symptomatic at less than ordinary levels of activity.
7. Unstable cardiac disease, including unstable angina or unstable hypertension, as defined by the need for change in medication for lack of disease control within 3 months of consent.
8. History or presence of sustained bradycardia (≤ 60 bpm) or history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or significant atrial tachyarrhythmias, as defined by the need for treatment.
tachyarrhythmias, as defined by the need for treatment.
9. Current treatment with agents that may prolong QT interval and may cause Torsade de Points which cannot be discontinued at least 2 weeks prior to treatment.
10. Known family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
11. Previous history of ≥ Grade 3 drug-induced QTc prolongation.
12. Screening 12-lead triplicate electrocardiogram (ECG) with an average measurable interval utilizing Fridericia's correction (QTcF) \>450 ms.
13. Inadequate liver function as demonstrated by:
* Serum bilirubin ≥ 1.5 times the upper limit of normal range (ULN); or
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5 times the ULN (up to 5 times the ULN in the presence of liver metastases).
14. Inability to tolerate oral medication.
15. Impaired coagulation as evidenced by:
1. International normalized ratio (INR) \>1.5 times ULN (or equivalent); or
2. Activated partial thromboplastin time (aPTT) \>1.5 times ULN.
16. Existing gastrointestinal disease affecting drug absorption, such as celiac disease or Crohn's disease.
17. Previous bowel resection that may impair study drug absorption.
18. Impaired renal function as demonstrated by creatinine clearance of ≤ 50 mL/min determined by Cockcroft Gault formula.
19. Absolute neutrophil count \<1.5 x 109/L, hemoglobin \<9.0 g/dL, platelet count \<100 x 109/L in the absence of blood product support.
20. Any evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the participant to participate in the study or which could jeopardize compliance with the protocol.
21. Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index.
22. Active, uncontrolled central nervous system (CNS) disease; (previously treated CNS metastases that are asymptomatic and do not require steroid treatment are allowed). Note: Participants with known CNS metastases who have completed radiotherapy at least 2 weeks prior to bemcentinib treatment are eligible.
23. Known active infection with human immunodeficiency virus (HIV), hepatitis B or C viruses (screening not required):
* Participants who have a history of hepatitis B infection are eligible provided they are hepatitis B surface antigen negative.
* Participants who have a history of hepatitis C infection are eligible provided they have no evidence of hepatitis C ribonucleic acid using a quantitative polymerase chain reaction assay at least 6 months after completing treatment for hepatitis C infection.
24. Major surgery requiring general anesthesia within 28 days prior to the start of bemcentinib, excluding biopsies and procedures for insertion of central venous access devices.
25. Treatment with cytotoxic chemotherapy, within the 3 weeks prior to the first dose of bemcentinib (Cycle 1, Day 1) with the exception of treatment with other EGFR inhibitors which must be completed 1 week prior to commencing treatment with bemcentinib. There is no requirement to discontinue ongoing treatment with erlotinib.
26. Treatment with other non-cytotoxic agents for NSCLC in the 10 days or 4 half-lives, prior to the first dose of bemcentinib (Cycle 1, Day 1) whichever is shorter.
27. Prior biological therapies in the 4 weeks or 5 half-lives, whichever is shorter before the first dose of bemcentinib (Cycle 1, Day 1). Note prior treatment with an alternative EGFR inhibitor and/or programmed cell death protein 1 (PD-1) blockade is permitted.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
BerGenBio ASA
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Dr. Lauren Byers, MD
Role: PRINCIPAL_INVESTIGATOR
MD, Anderson Cancer Centre Houston, Texas
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
UC San Diego Moores Cancer Center
La Jolla, California, United States
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
Moffitt Cancer Center
Tampa, Florida, United States
Horizon Oncology Research,
Lafayette, Indiana, United States
Henry Ford Health System
Detroit, Michigan, United States
The Sarah Cannon Research Institute Tennessee Oncology PLLC
Nashville, Tennessee, United States
Mary Crowley Cancer Research Centers
Dallas, Texas, United States
Southwestern Medical Center
Dallas, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
Oncology Consultants PA
Houston, Texas, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Hector A, Montgomery EA, Karikari C, Canto M, Dunbar KB, Wang JS, Feldmann G, Hong SM, Haffner MC, Meeker AK, Holland SJ, Yu J, Heckrodt TJ, Zhang J, Ding P, Goff D, Singh R, Roa JC, Marimuthu A, Riggins GJ, Eshleman JR, Nelkin BD, Pandey A, Maitra A. The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther. 2010 Nov 15;10(10):1009-18. doi: 10.4161/cbt.10.10.13248. Epub 2010 Nov 15.
Brand TM, Iida M, Stein AP, Corrigan KL, Braverman CM, Luthar N, Toulany M, Gill PS, Salgia R, Kimple RJ, Wheeler DL. AXL mediates resistance to cetuximab therapy. Cancer Res. 2014 Sep 15;74(18):5152-64. doi: 10.1158/0008-5472.CAN-14-0294. Epub 2014 Aug 18.
Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, Shen L, Fan Y, Giri U, Tumula PK, Nilsson MB, Gudikote J, Tran H, Cardnell RJ, Bearss DJ, Warner SL, Foulks JM, Kanner SB, Gandhi V, Krett N, Rosen ST, Kim ES, Herbst RS, Blumenschein GR, Lee JJ, Lippman SM, Ang KK, Mills GB, Hong WK, Weinstein JN, Wistuba II, Coombes KR, Minna JD, Heymach JV. An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin Cancer Res. 2013 Jan 1;19(1):279-90. doi: 10.1158/1078-0432.CCR-12-1558. Epub 2012 Oct 22.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
Ishikawa M, Sonobe M, Nakayama E, Kobayashi M, Kikuchi R, Kitamura J, Imamura N, Date H. Higher expression of receptor tyrosine kinase Axl, and differential expression of its ligand, Gas6, predict poor survival in lung adenocarcinoma patients. Ann Surg Oncol. 2013 Dec;20 Suppl 3(Suppl 3):S467-76. doi: 10.1245/s10434-012-2795-3. Epub 2012 Dec 16.
Korshunov VA. Axl-dependent signalling: a clinical update. Clin Sci (Lond). 2012 Apr;122(8):361-8. doi: 10.1042/CS20110411.
Liu L, Greger J, Shi H, Liu Y, Greshock J, Annan R, Halsey W, Sathe GM, Martin AM, Gilmer TM. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res. 2009 Sep 1;69(17):6871-8. doi: 10.1158/0008-5472.CAN-08-4490. Epub 2009 Aug 11.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
Zhang Z, Lee JC, Lin L, Olivas V, Au V, LaFramboise T, Abdel-Rahman M, Wang X, Levine AD, Rho JK, Choi YJ, Choi CM, Kim SW, Jang SJ, Park YS, Kim WS, Lee DH, Lee JS, Miller VA, Arcila M, Ladanyi M, Moonsamy P, Sawyers C, Boggon TJ, Ma PC, Costa C, Taron M, Rosell R, Halmos B, Bivona TG. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 2012 Jul 1;44(8):852-60. doi: 10.1038/ng.2330.
Thiele S, Baschant U, Rauch A, Rauner M. Instructions for producing a mouse model of glucocorticoid-induced osteoporosis. Bonekey Rep. 2014 Jul 2;3:552. doi: 10.1038/bonekey.2014.47. eCollection 2014.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
Access external resources that provide additional context or updates about the study.
Please see BerGenBio's website for more information.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
BGBC004
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.