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Lung Cancer MetastaticPhase 2NCT03184571

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

A Phase 2 study testing Pembrolizumab and Bemcentinib in people with Lung Cancer Metastatic and NSCLC Stage IV, run by BerGenBio ASA at 13 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab and Bemcentinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
99 participants
Where
13 sitesin 4 countries
Study dates
2 Oct 2017to 27 Oct 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • Must have had disease control containing at least 2 doses of anti-PD-(L)1 therapy. Disease control was defined as:
  • 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:
  • 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.
  • Patients (both male and female) of reproductive potential had to be willing to practice highly effective methods of contraception throughout the study and for 120 days after the last dose of study treatment. Abstinence was acceptable if this was the usual lifestyle for the patient. Female patients were considered NOT of childbearing potential if they had a history of surgical sterility or evidence of post-menopausal status defined as any of the following:
  • ≥45 years of age and not having menses for more than 1 year.
  • Amenorrheic for <2 years without a hysterectomy and oophorectomy and a follicle stimulating hormone (FSH) value in the post-menopausal range upon Screening evaluation.
  • Post-hysterectomy, oophorectomy, or tubal ligation; documented hysterectomy or oophorectomy had to be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation had to be confirmed with medical records of the actual procedure.
  • Had resolution of toxic effect(s) of the most recent prior cancer therapy to Grade 1 or less (except alopecia). If patient received major surgery or radiation therapy of >30 Gy, they had to have recovered from the toxicity and/or complications from the intervention.

Who cannot join

  • 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:
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  • 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.
  • Had a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Had a history of interstitial lung disease.
  • Inability to swallow or tolerate oral medication.
  • Existing gastrointestinal disease affecting drug absorption, such as celiac disease or Crohn's disease, or previous bowel resection, which was considered to be clinically significant or could interfere with absorption.
  • Known lactose intolerance.
  • Required vitamin K antagonists.
  • Treatment with any of the following: proton pump inhibitors or antacids within 7 days of the start of the study.
  • Treatment with any medication that was predominantly metabolized by CYP3A4 and had a narrow therapeutic index.
  • Known severe hypersensitivity (≥ Grade 3) to bemcentinib, pembrolizumab, and/or any of their excipients.
  • Any evidence of severe or uncontrolled systemic conditions (eg, severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions or ongoing.
  • Had active infection requiring systemic therapy (apart from cutaneous infections)
  • Had received radiation to the lung of >30 Gy within 6 months of the first dose.
  • Had a history or current evidence of any condition, therapy, or laboratory abnormality that could confound the results of the study, interfere with the patient's participation for the full duration of the study, or mean it was not in the best interest of the patient to participate, in the opinion of the Investigator.
  • Was pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting from Screening through to 120 days after the last dose of study treatment.
  • Had known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • Cohorts B and C: Had an EGFR mutation or ALK genomic rearrangement.
  • Had received an allogeneic tissue/solid organ transplant.

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

Spain8 sites

  • Hospital Teresa Herrera

    A Coruña, 15006

  • Hospital Universitari Germans Trias i Pujol-ICO

    Barcelona, Badalona, 08916

  • Servicio de Oncologia Hospital del Mar

    Barcelona, 08003

  • Hospital Universitario Vall d'Hebron (VHIR)

    Barcelona, 08035

  • Hospital Clinic Barcelona

    Barcelona, 08036

  • Hospital Universitario Fundacion Jimene Diaz

    Madrid, 28040

  • Hospital Universitario 12 de Octubre, Servicio de oncologia

    Madrid, 28041

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

Other trials in Spain

United States2 sites

  • Dartmouth-Hitchcock Medical Center (DHMC)

    Lebanon, New Hampshire, 03756

  • Medical College of Wisconsin, 9200 W Wisconsin Avenue

    Milwaukee, Wisconsin, 53226-3522

Other trials in United States

United Kingdom2 sites

  • Guy's and St Thomas' NHS Foundation Trust

    London, SE1 9RT

  • Christie NHS Hospital Foundation Trust

    Manchester, M20 4BX

Other trials in United Kingdom

Norway1 site

  • Radiumhospitalet, Oslo University Hospital PB

    Oslo, 0424

Other trials in Norway

About this study

Official title: A Phase II Multi Center Study of BGB324 in Combination With Pembrolizumab in Patients With Previously Treated Advanced Adenocarcinoma of the Lung

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.

Being tested
Pembrolizumab, Bemcentinib
Keywords
bemcentinib, NSCLC, pembrolizumab, Keytruda, BGB324
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Adenocarcinoma of Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Keytruda

    Pembrolizumab is a PD-1 inhibitor

  • BemcentinibDrug

    Also called BGB324

    Bemcentinib is a selective Axl kinase inhibitor;

Study groups in NCT03184571
Study groupRoleWhat they receive
Cohort A Bemcentinib + pembrolizumabExperimentalCohort 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.
Receives: Drug: Pembrolizumab; Drug: Bemcentinib
Cohort B Bemcentinib + pembrolizumabExperimentalCohort 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).
Receives: Drug: Pembrolizumab; Drug: Bemcentinib
Cohort C Bemcentinib + pembrolizumabExperimentalCohort 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.
Receives: Drug: Pembrolizumab; Drug: Bemcentinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Disease Control Rate

    Disease Control Rate includes all participants who have a partial or complete response, or who maintain stable disease.

    Measured: 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.

  2. Duration of Response

    Duration of response includes participants with a partial or complete response and is measured from the date of response until the cancer progresses (worsens).

    Measured: 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.

  3. Progression-free Survival (PFS)

    PFS is measured from the date of the 1st dose of the 1st cycle until the date of progression (the date on which the progression is initially observed) or the date of death (whichever is earlier).

    Measured: 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)

  4. Overall Survival

    Time to death is measured from the date of first dose until the date of death or the date the participants is last known to be alive. It includes all participants.

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

  5. Number of Participants With Adverse Events (AEs)

    The number of participants with each adverse event (AE) will be summarized.

    Measured: 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.

  6. Pharmacokinetic (PK) Parameters: Maximum Observed Concentration (Cmax)

    Cmax defined as the maximum observed concentration. These Cmax results are after the maintenance dose.

    Measured: Up to 106 weeks

  7. PK Parameters: Area Under the Curve (AUC)

    AUC defined as the area under the concentration versus time curve. Measured as AUC 0-24h, area under the concentration versus time curve from time 0 to 24 hours post-dose at steady state following the maintenance dose per cohort.

    Measured: Cycle 1 Day 1 and Day 3 pre-dose, and 2, 4, 6, 8 hours post-dose; Cycle 1 Day 2 , Day 4 ,Day 8 and Day 15 pre-dose; Cycle 2 Day 1, and Cycle 3 Day 1., pre-dose. Each cycle is 21 days in duration.

  8. PK Parameters: Elimination Half-life (T½)

    T½ defined as the elimination half-life. Measured at steady state following the maintenance dose per cohort.

    Measured: Up to 106 weeks

  9. Frequency of Clinical Laboratory, Vital Signs, and Electrocardiogram (ECG) Abnormalities.

    Number of events (Frequency) of clinically significant laboratory (hematology, including coagulation, urinalysis), vital signs (temperature, systolic blood pressure, diastolic blood pressure, heart rate, and respiratory rate), and ECG abnormalities.

    Measured: Up to 106 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2017
  2. Study start2 Oct 2017
  3. Primary completion27 Oct 2022
  4. Study completion27 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
Extension to Simon's 2-stage design allowing termination at the end of Stage 1 for either futility or efficacy.
Masking
None (open label)
Enrolment
99 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03184571
Sponsor's protocol ID
BGBC008
Other IDs
MK-3475 PN531, 2016-003609-32, 2016
Status last verified
Sep 2025
First submitted
30 May 2017
Last updated
25 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie the results reported in the article, after deidentification \[text, tables, figures and appendices\].

Publications

  • 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.

    PubMed 35492873

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Bemcentinib in people with Lung Cancer Metastatic and NSCLC Stage IV, run by BerGenBio ASA at 13 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Spain, United States, United Kingdom, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03184571, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025.

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