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

Exclusion Criteria

• •1. Had disease suitable for local therapy administered with curative intent.
• •2. 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.
• •3. 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.
• •4. 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.
• •5. 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.
• •6. History of the following cardiac conditions:
• •1. Congestive cardiac failure of \> Grade II severity according to the New York Heart Association (defined as symptomatic at less than ordinary levels of activity).
• •2. Ischemic cardiac event including, myocardial infarction, within 3 months before the first dose.
• •3. 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.
• •4. 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.
• •5. 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).
• •7. 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).
• •8. 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.
• •9. Screening 12-lead electrocardiogram (ECG) with a measurable QTc interval according to Fridericia's correction \>450 msec.
• •10. 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.
• •11. Had participated in a study involving any immune checkpoint inhibitor other than currently approved immune checkpoint inhibitors for their lung cancer.
• •12. 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.
• •13. 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.
• •14. 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.
• •15. 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.
• •16. 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.
• •17. Active autoimmune disease that had required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs);
• •18. Known history of human immunodeficiency virus (HIV 1/2 antibodies).
• •19. Had known active infection with hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, hepatitis C virus RNA \[qualitative\] was detected).
• •20. Had received a live-virus vaccination within 30 days of planned treatment start.
• •21. Had a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• •22. Had a history of interstitial lung disease.
• •23. Inability to swallow or tolerate oral medication.
• •24. 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.
• •25. Known lactose intolerance.
• •26. Required vitamin K antagonists.
• •27. Treatment with any of the following: proton pump inhibitors or antacids within 7 days of the start of the study.
• •28. Treatment with any medication that was predominantly metabolized by CYP3A4 and had a narrow therapeutic index.
• •29. Known severe hypersensitivity (≥ Grade 3) to bemcentinib, pembrolizumab, and/or any of their excipients.
• •30. Any evidence of severe or uncontrolled systemic conditions (eg, severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions or ongoing.
• •31. Had active infection requiring systemic therapy (apart from cutaneous infections)
• •32. Had received radiation to the lung of \>30 Gy within 6 months of the first dose.
• •33. 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.
• •34. 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.
• •35. Had known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• •36. Cohorts B and C: Had an EGFR mutation or ALK genomic rearrangement.
• •37. Had received an allogeneic tissue/solid organ transplant.