Randomised, Double-Blinded, Placebo Controlled, Phase 2 Study of CS-1008 in Combination With Carboplatin/Paclitaxel in Chemotherapy naïve Subjects With Metastatic or Unresectable Non-small Cell Lung Cancer
- At least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Measurable disease as defined by RECIST criteria
- Adequate organ and bone marrow function as evidenced by:
- Hemoglobin >= 9 g/dL;
- ANC >= 1.5 x 109/L;
- Platelet count >= 100 x 109/L;
- Serum creatinine < 1.5 mg/dL or creatinine clearance > 60 mL/min;
- AST, ALT, and alkaline phosphatase <= 2.5 x upper limit of normal (ULN) if
without liver metastasis and <= 5.0 x ULN if liver metastasis;
- Total bilirubin <= 2.0 x ULN.
- Men and women of childbearing potential must be willing to consent to using effective
double barrier contraception (eg, hormonal contraceptives, bilateral tubal ligation,
barrier with spermicidal, intrauterine device) while on treatment and for 3 months
- All female subjects of childbearing potential must have a negative pregnancy test
(serum or urine) result <= 72 hours before initiating study treatment.
- Subjects must be fully informed about their illness and the investigational nature of
the study protocol (including foreseeable risks and possible side effects) and must
sign and date an IEC approved ICF before performance of any study specific procedures
- Anticipation of need for a major surgical procedure or radiotherapy (RT) during the
- Prior treatment with chemotherapy for their disease.
- History of any of the following conditions within 6 months before study enrolment:
myocardial infarction; New York Heart Association (NYHA) class II or higher
severe/unstable angina pectoris; coronary/peripheral artery bypass graft; NYHA class
III or IV congestive heart failure; cerebrovascular accident or transient ischemic
attack, pulmonary embolism, or other clinically significant thromboembolic event;
clinically significant pulmonary disease (eg, severe chronic obstructive pulmonary
disease or asthma); clinically significant pulmonary edema or anasarca.. See Section
17.2 for NYHA Classification.
- Clinically significant pleural or pericardial effusions.
- Grade 2 or higher current peripheral neuropathy (See Section 17.3; NCI CTCAE, Version
- Clinically active brain metastasis (ie, untreated, still requiring therapy with
steroids or RT, or with progression within 4 weeks after completion of RT); an
uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis.
- History of malignancy other than NSCLC, unless there is the expectation that the
malignancy has been cured, and tumor specific treatment for the malignancy has not
been administered within the previous 5 years.
- Clinically significant active infection that requires antibiotic therapy or Human
Immunodeficiency Virus (HIV) positive subjects receiving antiretroviral therapy.
- Previous treatment with chemotherapy, CS 1008, other agonistic DR 5 or DR 4
antibodies, or with TRAIL.
- Pregnant or breast feeding.
- Known history of hypersensitivity reactions to any of the components of CS 1008,
carboplatin, or paclitaxel formulations.
- Serious intercurrent medical or psychiatric illnesses or any other conditions that in
the opinion of the Investigator would impair the ability to give informed consent or
unacceptably reduce protocol compliance or safety of the study treatment.