A clinical study of bemcentinib with standard of care chemoimmunotherapy in untreated advanced/metastatic non-small cell lung cancer patients with a mutation in the STK11 gene

Prior treatment

• Has received any prior chemotherapy or biological therapy for advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they are radiologically stable, i.e. without evidence of progression for at least 2 weeks and have no evidence of new or enlarging brain metastases and are off steroids 7 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Subjects with asymptomatic brain metastases (i.e. no neurological symptoms, no requirements for corticosteroids, and no lesion >1.5cm) may participate but will require regular imaging of the brain as a site of disease. Subjects who have experienced an acute neurological event (e.g. intracranial or subarachnoid haemorrhage, stroke, intracranial trauma) within 6 months prior to study enrolment will be excluded.

Other illness

• Has a known history of prior malignancy except if the subject has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy.

Lab values

• History of the following cardiac conditions: a. Congestive cardiac failure of >Grade II severity according to the New York Heart Association (NYHA) or resistant or inadequately treated heart failure. b. Ischemic cardiac event including myocardial infarction or hospitalization for unstable angina within 3 months prior to first dose. c. Abnormal left ventricular ejection fraction on echocardiography or multigated acquisition scan (MUGA) (less than the lower limit of normal for a subject of that age at the treating institution or <45%, whichever is lower), or history of cardiomyopathy or left ventricular hypertrophy. d. Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (i.e. sustained systolic blood pressure (BP) >160 mmHg or diastolic BP >90 mmHg), or need to change medication due to lack of disease control within 12 weeks prior to the provision of consent. e. History or presence of sustained bradycardia (≤55 bpm) or history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or significant arrhythmias or any conduction disorder within 6 months prior to dosing as defined by the need for treatment. f. Family history of long QTc syndrome or ventricular arrhythmias; personal history of long QTc syndrome or previous drug induced QTc prolongation of at least Grade 3 (QTc >500ms). g. Presence of any other risk factors that increase the risk of QTc prolongation, specifically, hypokalemia or hypomagnesemia (if corrected the subject may be enrolled) or inadequately treated hypothyroidism (defined as thyroid stimulating hormone (TSH) below the expected range). h. Current treatment with any agent known to cause QT prolongation and have a risk for Torsades de pointes (TdP), which cannot be discontinued at least 5 and ½ half-lives or 2 weeks prior to the first dose of study treatment, with the exception of antiemetics (e.g. ondansetron) which may be required. Please see https://crediblemeds.org for a list of medications with known Torsade de Point risk that need to be excluded.

Other

• Has any actionable mutation that is considered targetable with first-line treatment.

• The subject (or legally acceptable representative, if applicable) must provide written informed consent for the study prior to any screening procedures.
• Be ≥ 18 years of age on the day of signing the informed consent.
• Have a histologically- or cytologically confirmed diagnosis of advanced (Stage IIIb/IIIc) or metastatic (Stage IV) (AJCC Edition 8) non-squamous NSCLC not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (Phase 1b).
• Have a histologically- or cytologically confirmed diagnosis of advanced (Stage IIIb/IIIC) or metastatic (Stage IV) (AJCC, Edition 8) non-squamous NSCLC with STK11m mutation, not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (Phase 2a).
• Participants who received prior neo-adjuvant or adjuvant/consolidation treatment (radiotherapy, chemotherapy, immunotherapy) or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months since the last dose of chemotherapy, immunotherapy and/or radiotherapy before enrollment.
• Have measurable disease per RECIST 1.1 as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.