Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

NCT03184571 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: BGBC008MK-3475 PN5312016-003609-32
• Study Type: interventional
• Target: 99
• Locations: 4 countries
• Sites: 13

Brief Summary

This is an open-label, multi-center, single arm, phase II study to assess the anti-tumor activity and safety of bemcentinib in combination with pembrolizumab in up to 106 participants with previously treated, advanced adenocarcinoma of the lung. The study will enrol three cohorts of participants with previously treated, advanced adenocarcinoma of the lung. Cohort A will consist of participants who received a maximum of 1 prior line of platinum-containing chemotherapy and no prior immunotherapy. Cohort B will consist of participants who received a maximum of one prior line of an anti-programmed death receptor (PD)-(L)1 therapy (monotherapy). Cohort C will consist of participants who received a maximum of one prior line of therapy with an anti-PD-(L)1 therapy in combination with a platinum-containing chemotherapy. The primary objective is to assess the anti-tumor activity of bemcentinib in combination with pembrolizumab.

Conditions

Lung Cancer Metastatic; NSCLC Stage IV; Adenocarcinoma of Lung

Keywords

bemcentinib; NSCLC; pembrolizumab; Keytruda; BGB324

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate (ORR) includes all participants who have a partial (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by CT scan or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions,. ORR was defined as the percentage of evaluable patients who had at least 1 confirmed overall response CR or PR according to modified RECIST 1.1 evaluation and definitions of disease response.

  The disease response is the best improvement or change in a participants cancer burden, as measured from baseline (screening) and then measured again at regular intervals over the whole period of the study, an average of 24 months.

Secondary Outcomes (9)

• Disease Control Rate

  Disease response is assessed every 9 weeks for the first 45 weeks and then every 12 weeks until disease progression (worsens) or study completion, an average of 24 months.

• Duration of Response

  Disease response is assessed every 9 weeks for the first 45 weeks and then every 12 weeks until disease progression or study completion, an average of 24 months.

• Progression-free Survival (PFS)

  Disease assessments are conducted at screening and then every 9 weeks for the first 45 weeks and then every 12 weeks until disease progression or death, whichever comes first, up to study completion (an average of 24 months)

• Overall Survival

  Survival visits are conducted every 12 weeks after disease progression until death or until study completion (an average of 24 months).

• Number of Participants With Adverse Events (AEs)

  Adverse events are collected from the date of consent until up to 120 days after cessation of both treatments, up to 24 months of treatment, followed by an additional 120 days following cessation, up to 27 months total.

Study Arms (3)

Cohort A Bemcentinib + pembrolizumab

EXPERIMENTAL

Cohort A bemcentinib (BGB324) in combination with pembrolizumab will be administered to participants with previously treated, advanced adenocarcinoma of the lung who received a maximum of 1 prior line of platinum-containing chemotherapy and no prior immunotherapy.

Drug: Pembrolizumab; Drug: Bemcentinib

Cohort B Bemcentinib + pembrolizumab

EXPERIMENTAL

Cohort B bemcentinib (BGB324) in combination with pembrolizumab will be administered to participants with previously treated, advanced adenocarcinoma of the lung who received a maximum of one prior line of an anti-PD-(L)1 therapy (monotherapy).

Drug: Pembrolizumab; Drug: Bemcentinib

Cohort C Bemcentinib + pembrolizumab

EXPERIMENTAL

Cohort C bemcentinib (BGB324) in combination with pembrolizumab will be administered to participants with previously treated, advanced adenocarcinoma of the lung who received a maximum of one prior line of therapy with an anti-PD-(L)1 therapy in combination with a platinum-containing chemotherapy.

Drug: Pembrolizumab; Drug: Bemcentinib

Interventions

Pembrolizumab DRUG

Pembrolizumab is a PD-1 inhibitor

Also known as: Keytruda

Cohort A Bemcentinib + pembrolizumab; Cohort B Bemcentinib + pembrolizumab; Cohort C Bemcentinib + pembrolizumab

Bemcentinib DRUG

Bemcentinib is a selective Axl kinase inhibitor;

Also known as: BGB324

Cohort A Bemcentinib + pembrolizumab; Cohort B Bemcentinib + pembrolizumab; Cohort C Bemcentinib + pembrolizumab

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 informed consent.
• Male and non-pregnant females who were aged 18 years or older at the time of provision of informed consent.
• Histopathologically or cytologically documented Stage IV adenocarcinoma NSCLC; Note: Patients with a mixed cell histology including a significant area of adenocarcinoma histology were eligible.
• Cohort A: Had disease progression on or after a prior platinum-containing chemotherapy; Note: Patients with EGFR mutations or ALK genomic rearrangements had to have documented disease progression on at least 1 licensed therapy for these indications and may not have received platinum-containing chemotherapy.
• Cohort B:
• Had received a maximum of 1 prior line of an anti-PD-(L)1 therapy (monotherapy).
• Must have had disease control containing at least 2 doses of anti-PD-(L)1 therapy. Disease control was defined as:
• i. Stable disease for at least 12 weeks (date of first progression on anti-PD-(L)1 therapy) Or ii. Confirmed PR or CR - confirmatory scan must have been performed \>4 weeks from initial scan) c) Had disease progression when entering Screening (first date of progression of disease was taken as end date of response to previous anti-PD-(L)1 therapy) and this must have been within 12 weeks of last dose of treatment containing an anti-PD-(L)1 therapy. Progression should have been confirmed in 1 of the following ways: i. Having had 2 scan assessments completed at least 4 weeks apart, both showing progression according to response evaluation criteria in solid tumors (RECIST) 1.113 or ii. Having had 1 scan assessment completed showing disease progression according to standards used for previous therapy combined with rapid disease progression / clinical progression.
• Cohort C:
• Had received a maximum of 1 prior line of an anti-PD-(L)1 therapy in combination with a platinum-containing chemotherapy.
• Must have had disease control containing at least 2 doses of anti-PD-(L)1 therapy. Disease control was defined as:
• i. Stable disease for at least 12 weeks (date of first progression on anti-PD-(L)1 therapy) Or ii. Confirmed PR or CR - confirmatory scan must be performed \>4 weeks from initial scan c) Had disease progression when entering Screening (first date of progression of disease was taken as end date of response to previous anti-PD-(L)1 therapy) and this must have been within 12 weeks of last dose of treatment containing an anti-PD-(L)1 therapy. Progression had to be confirmed in 1 of the following ways: i. Having had 2 scan assessments completed at least 4 weeks apart, both showing progression according to RECIST 1.113 or ii. Having had 1 scan assessment completed showing disease progression according to standards used for previous therapy combined with rapid disease progression/clinical progression
• Measurable disease as defined by RECIST 1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) and as determined by the site study team; tumor lesions situated in a previously irradiated area were considered measurable if progression had been demonstrated in such lesions.
• Provision of suitable tumor tissue for the analysis of AXL kinase expression and PD-L1 expression; suitable tumor tissue had to consist of a minimum of a newly acquired (fresh) tumor tissue sample (as a formalin-fixed paraffin-embedded \[FFPE\] block), together with either further newly acquired tumor tissue (ie, further FFPE block) or an archival tumor tissue sample (as a further FFPE block or further 10 unstained slides).
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1

You may not qualify if:

• Had disease suitable for local therapy administered with curative intent.
• Had received more than 1 prior line of chemotherapy for advanced or metastatic adenocarcinoma of the lung. For all cohorts: Note: Patients may have received additional prior radiotherapy or chemotherapy in the adjuvant setting, providing it was completed at least 6 months prior to start of study treatment.
• Cohort A: Had received prior therapy with an immunomodulatory agent; Cohort B: Had received prior chemotherapy alone or in combination with immunotherapy in the metastatic setting.
• Had a known additional malignancy that was progressing or required active treatment; Note: Exceptions included basal cell carcinoma of the skin, squamous cell carcinoma of the skin that had undergone potentially curative therapy, or in situ cervical cancer.
• Had known active central nervous system (CNS) metastases and/or carcinomatous meningitis; Note: Patients with previously treated brain metastases could participate provided they were stable (without evidence of progression by scans \[using the identical modality for each assessment, either MRI or CT scan\] for at least 4 weeks prior to the first dose of study treatment and any neurological symptoms had returned to Baseline), having no evidence of new or enlarging brain metastases, and were not using steroids for at least 7 days prior to study treatment.
• History of the following cardiac conditions:
• Congestive cardiac failure of \> Grade II severity according to the New York Heart Association (defined as symptomatic at less than ordinary levels of activity).
• Ischemic cardiac event including, myocardial infarction, within 3 months before the first dose.
• Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (ie, sustained systolic blood pressure (BP) \>160 mm Hg or diastolic BP \>90 mm Hg), or need to change medication because of lack of disease control within 6 weeks before the provision of consent.
• History or presence of sustained bradycardia (≤55 beats per minute), left bundle branch block, cardiac pacemaker, or ventricular arrhythmia; Note: Patients with a supraventricular arrhythmia requiring medical treatment but with a normal ventricular rate were eligible.
• Family history of long QTc syndrome, personal history of long QTc syndrome, or previous drug-induced QTc prolongation of at least Grade 3 (QTc \>500 msec).
• Abnormal left ventricular ejection fraction on echocardiography or multigated acquisition scan (MUGA) (less than the lower limit of normal for a patient of that age at the treating institution or \<45%, whichever was lower).
• Current treatment with any agent known to cause Torsades de Pointes which could not be discontinued at least 5 half-lives or 2 weeks prior to the first dose of study treatment.
• Screening 12-lead electrocardiogram (ECG) with a measurable QTc interval according to Fridericia's correction \>450 msec.
• Was currently participating and receiving study therapy or had participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.

Sponsors & Collaborators

• BerGenBio ASA: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (13)

Dartmouth-Hitchcock Medical Center (DHMC)

Lebanon, New Hampshire, 03756, United States

Location

Medical College of Wisconsin, 9200 W Wisconsin Avenue

Milwaukee, Wisconsin, 53226-3522, United States

Location

Radiumhospitalet, Oslo University Hospital PB

Oslo, 0424, Norway

Location

Hospital Universitari Germans Trias i Pujol-ICO

Barcelona, Badalona, 08916, Spain

Location

Hospital Teresa Herrera

A Coruña, 15006, Spain

Location

Servicio de Oncologia Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Vall d'Hebron (VHIR)

Barcelona, 08035, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Fundacion Jimene Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre, Servicio de oncologia

Madrid, 28041, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Christie NHS Hospital Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Li H, Liu Z, Liu L, Zhang H, Han C, Girard L, Park H, Zhang A, Dong C, Ye J, Rayford A, Peyton M, Li X, Avila K, Cao X, Hu S, Alam MM, Akbay EA, Solis LM, Behrens C, Hernandez-Ruiz S, Lu W, Wistuba I, Heymach JV, Chisamore M, Micklem D, Gabra H, Gausdal G, Lorens JB, Li B, Fu YX, Minna JD, Brekken RA. AXL targeting restores PD-1 blockade sensitivity of STK11/LKB1 mutant NSCLC through expansion of TCF1+ CD8 T cells. Cell Rep Med. 2022 Mar 15;3(3):100554. doi: 10.1016/j.xcrm.2022.100554. eCollection 2022 Mar 15.

  PMID: 35492873 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung

Interventions

pembrolizumab; bemcentinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: BerGenBio Clinical Team
• Organization: BerGenBio ASA

registry.postings@bergenbio.com

+47 559 61 159

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Extension to Simon's 2-stage design allowing termination at the end of Stage 1 for either futility or efficacy.

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 12, 2017
• Study Start: October 2, 2017
• Primary Completion: October 27, 2022
• Study Completion: October 27, 2022
• Last Updated: September 25, 2025
• Results First Posted: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Proposal should be directed to clinical@bergenbio.com. To gain access, data requestors will need to sign a data access agreement.

Locations

GB (2); NO (1); US (2); ES (8)