- Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC
(Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and
Drug Administration (FDA) approved FISH assay (Abbott Molecular Inc) or by
Immunohistochemistry (IHC) (Ventana Inc), or a ROS1 rearrangement as determined by
FISH or RT PCR or Next Generation Sequencing (NGS) via a local diagnostic test (LDT).
All patients (ALK positive and ROS1 positive) must have archival tissue sample
available and collected prior to enrollment.
- Disease Status Requirements:
Phase 1: ALK-positive NSCLC and ROS1-positive patients must either be treatment naïve in
the advanced setting or have had disease progression after at least 1 previous ALK/ROS1
inhibitor therapy(ies).
Phase 2:
ALK-positive NSCLC patients must either be or have had:
- Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no
prior ALK inhibitor therapy allowed).
- Disease progression after crizotinib only. No prior chemotherapy is allowed in the
metastatic disease setting.
- Disease progression after crizotinib and 1 or 2 prior regimens of chemotherapy in the
metastatic disease setting.
- Disease progression after 1 prior ALK inhibitor therapy other than crizotinib.
Patients may have had any number of prior chemotherapy regimens in any disease
setting.
- Disease progression after 2 prior ALK inhibitor therapies. Patients may have had any
number of prior chemotherapy regimens in any disease setting.
- Disease progression after 3 prior ALK inhibitor therapies. Patients may have had any
number of prior chemotherapy regimens in any disease setting.
ROS1-positive NSCLC patients may be:
- Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no
prior ROS inhibitor therapy).
- Any number of prior therapies (ie, chemotherapy and/or ROS inhibitor therapies).
- Tumor Requirements:
All Patients must have at least one measurable target extracranial lesion according to
RECIST v1.1. In addition patients with asymptomatic CNS metastases (including patients
asymptomatic by means of stable or decreasing doses of steroids within the last 2 weeks
prior to study entry) will be eligible. Patients who have leptomeningeal disease (LM) or
carcinomatous meningitis (CM) are eligible.
- Adequate Bone Marrow, Pancreatic Function, Renal Function and Liver Function.
- Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study
entry. Whole brain radiation must have completed at least 4 weeks prior to study
entry.
- Systemic anti cancer therapy completed within a minimum of 5 half lives of study
entry.
- Prior therapy with an antibody or drug specifically targeting T-cell co-stimulation or
immune checkpoint pathways, including, but not limited to, anti-PD-1, anti-PD-L1,
anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4
(anti-CTLA-4) antibody.
- Active and clinically significant bacterial, fungal, or viral infection including
hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or
acquired immunodeficiency syndrome (AIDS) related illness.
- Clinically significant cardiovascular disease (that is, active or
enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable
angina, congestive heart failure (New York Heart Association Classification Class ?
II), second-degree or third-degree AV block (unless paced) or any AV block with PR
>220 msec. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ?2, uncontrolled atrial
fibrillation of any grade, bradycardia defined as
healthy such as long-distance runners, etc.), machine-read ECG with QTc >470 msec, or
congenital long QT syndrome.
- History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial
fibrosis or interstitial lung disease including a history of pneumonitis,
hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease,
obliterative bronchiolitis and pulmonary fibrosis.
- Current use or anticipated need for food or drugs that are known strong or moderate
CYP3A4 inhibitors, inducers and substrates; drugs that are CYP2C9 substrates; drugs
that are sensitive CYP2B6 substrates; drugs that are strong CYP2C19 inhibitors; drugs
that are strong CYP2C8 inhibitors; and drugs that are P-gp substrates.