A Phase 1 Dose-Escalation Study of XL147 (SAR245408) in Combination With Erlotinib in Subjects With Solid Tumors
- Subjects accrue to one of two phases:
- in the Dose Escalation Phase, the subject has a histologically confirmed solid
tumor that is metastatic or unresectable and is no longer responding to
therapies known to prolong survival or to other standard therapies, or has
disease for which no standard therapy exists or for which monotherapy with
erlotinib is considered standard therapy.
- in the Cohort Expansion Phase, the subject has advanced or metastatic NSCLC that
is no longer responding to therapies known to prolong survival or to other
standard therapies and which:
1. has been previously or currently treated with erlotinib or gefitinib or
2. with the agreement of the sponsor, has been previously or is currently
treated with other EGFR/VEGFR tyrosine kinase inhibitors
- The subject has measurable or non-measurable lesions by the Response Evaluation
Criteria in Solid Tumor (RECIST) criteria.
- At least 10 unstained slides of tumor tissue, archival or fresh, or paraffin block or
a fresh tumor biopsy are identified and designated for central laboratory analysis.
- The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- The subject has adequate organ and marrow function.
- The subject has a fasting plasma glucose ≤ 120 mg/dL at screening.
- The subject is ≥ 18 years old.
- The subject is capable of understanding and complying with the protocol requirements
and has signed the informed consent document.
- Sexually active subjects (male and female) must use accepted methods of contraception
during the course of the study and for at least 3 months after the last dose of
- Female subjects of childbearing potential must have a negative pregnancy test at
- The subject has previously been treated with a selective PI3K inhibitor.
- The subject has received:
- cytotoxic chemotherapy (including investigational cytotoxic agents) or biologic
agents (antibodies, immune modulators, cytokines) within 3 weeks or has received
nitrosoureas or mitomycin C within 6 weeks before the scheduled first dose of
- a small-molecule kinase inhibitor (including investigational small molecule
kinase inhibitors) excluding small-molecule inhibitors of EGFR or non-cytotoxic
hormonal agent within 14 days of the scheduled first dose of XL147
- other investigational therapy (ie, not specified in exclusion criterion) within
28 days of the first scheduled dose of XL147
- The subject has not recovered from toxicity due to prior therapy to baseline or
Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or less (except
- The subject has a diagnosis of uncontrolled diabetes mellitus.
- The subject is currently receiving anticoagulation with therapeutic doses of warfarin
(low-dose warfarin ≤ 1mg/day, heparin, and low-molecular weight heparins are
- The subject is taking oral corticosteroids chronically.
- The subject has prothrombin time/International Normalized Ratio and/or partial
thromboplastin time test results at screening that are above 1.3x the laboratory
upper limit of normal.
- The subject has uncontrolled intercurrent illness including but not limited to an
active infection or hypertension that would limit compliance with study requirements.
- The subject has had congestive heart failure, unstable angina, a myocardial
infarction, or a stroke within 3 months of entering the study.
- The subject has a baseline corrected QT interval (QTc) ≥ 460 ms.
- The subject has psychiatric illness/social situation(s) that would limit compliance
with study requirements.
- The subject is known to be positive for the human immunodeficiency virus.
- The subject has a previously identified allergy or hypersensitivity to components of
the XL147 formulation.
- The subject is pregnant or breastfeeding.
- The subject is unable or unwilling to abide by the study protocol or cooperate fully
with the investigator or designee.