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

Completed · Phase 2

Conditions studied: Lung Cancer Metastatic, NSCLC Stage IV, Adenocarcinoma of Lung

In brief

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.

Key facts

Study ID

NCT03184571

Run by

BerGenBio ASA

People needed

99

Starts

2017-10-02

Expected to finish

2022-10-27

Last updated by the study team

2025-09-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Life expectancy of at least 3 months
• Adequate organ function confirmed at Screening within 10 days of treatment initiation as evidenced by:
• Platelet count ≥100,000/mm3
• Hemoglobin ≥9.0 g/dL (≥5.6 mmol/L)
• Absolute neutrophil count >1,500/mm3
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × the upper limit of normal (ULN), or ≤5 × the ULN for patients with liver metastases
• Total bilirubin ≤1.5 × the ULN, or direct bilirubin < ULN for patients with total bilirubin levels >1.5 ULN
• Creatinine ≤1.5 × the ULN or calculated creatinine clearance 60 mL/min (by Cockcroft Gault formula)
• International normalized ratio or prothrombin time ≤1.5 × the ULN and activated partial thromboplastin time ≤1.5 × the ULN; Note: If patient was receiving anticoagulant therapy, then prothrombin time or partial thromboplastin time had to be within the therapeutic range of intended use of anticoagulants.
• Female patients of childbearing potential had to have a negative urine or serum pregnancy test within 72 hours before the first dose of study treatment. If the urine test was positive or could not be confirmed as negative, a serum pregnancy test was required.

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.
• Had participated in a study involving any immune checkpoint inhibitor other than currently approved immune checkpoint inhibitors for their lung cancer.
• Received chemotherapy or targeted small-molecule therapy or radiation therapy within 2 weeks before starting study treatment or who had not recovered (ie, ≤ Grade 1 at Baseline) from adverse events (AEs) due to a previously administered agent.
• Received an anti-cancer mAb within 4 weeks prior to the first dose of study treatment or who had not recovered (ie, ≤ Grade 1 or Baseline) from AEs due to agents administered more than 4 weeks earlier.
• Major surgery within 28 days before start of study treatment and failure to have recovered adequately from the toxicity and/or complications from the intervention prior to the first dose of study treatment.
• Received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (CSFs) (including granulocyte-CSF, granulocyte macrophage-CSF, or recombinant erythropoietin) within 4 weeks prior to the first dose of study treatment.
• Had a diagnosis of immunodeficiency or was receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment; Note: The use of physiologic doses of corticosteroids could have been approved after consultation with the Sponsor.
• Active autoimmune disease that had required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs);
• Known history of human immunodeficiency virus (HIV 1/2 antibodies).
• Had known active infection with hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus RNA [qualitative] was detected).
• Had received a live-virus vaccination within 30 days of planned treatment start.

Where it is running

• Dartmouth-Hitchcock Medical Center (DHMC) — Lebanon, New Hampshire, United States
• Medical College of Wisconsin, 9200 W Wisconsin Avenue — Milwaukee, Wisconsin, United States
• Radiumhospitalet, Oslo University Hospital PB — Oslo, Norway
• Hospital Universitari Germans Trias i Pujol-ICO — Barcelona, Badalona, Spain
• Hospital Teresa Herrera — A Coruña, Spain
• Servicio de Oncologia Hospital del Mar — Barcelona, Spain
• Hospital Universitario Vall d'Hebron (VHIR) — Barcelona, Spain
• Hospital Clinic Barcelona — Barcelona, Spain
• Hospital Universitario Fundacion Jimene Diaz — Madrid, Spain
• Hospital Universitario 12 de Octubre, Servicio de oncologia — Madrid, Spain
• Hospital Universitario Virgen de la Victoria — Málaga, Spain
• Guy's and St Thomas' NHS Foundation Trust — London, United Kingdom
• Christie NHS Hospital Foundation Trust — Manchester, United Kingdom

Full record on ClinicalTrials.gov

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