This is a Phase iii, multicenter, randomized, double-blind trial of bavituximab plus docetaxel or placebo plus docetaxel in patients with previously treated stage iiib/iV non-squamous nSCLC.
eligible patients will be randomized to receive 3 mg/kg bavituximab or placebo intravenously (iV) once weekly in combination with docetaxel iV for up to six 21-day cycles. Patients will be stratified by region(north america, europe, or Rest of World), disease stage (iiib or iV), and previous maintenance/targeted therapy (yes or no), a surrogate for presence of epidermal growth factor receptor (eGFR)-activating mutations or anaplastic lymphoma kinase (aLK) translocations. Study visits will occur every week for blinded treatment(bavituximab or placebo) administration; docetaxel administration will occur on Day 1 of each cycle for up to 6 cycles. The day of docetaxel administration is Day 1 of each combination therapy cycle.
Serial assessments of safety and efficacy will be performed as outlined in the Schedule of Visits and Procedures. These assessments will include evaluations of adverse events (aes). Complete blood counts(CBCs) and biochemistry will be obtained prior to the start of each treatment cycle and more frequently at the investigator's discretion during treatment cycles. Tumor response will be assessed radiographically after every 2 cycles during combination therapy. Patients with equivocal radiological progression using modified Response evaluation Criteria in Solid Tumors (ReCiST) may continue on study treatment if the investigator's assessment is that the patient is experiencing clinical benefit and tolerating the treatment. if there is clear radiological evidence of disease progression confirmed by central review using modified ReCiST (eg, one or more new lesions over 1.5 cm in short axis for lymph nodes or 1 cm in long axis for non-nodal lesions), rapid tumor progression or clinical progression with symptoms that require urgent medical intervention (eg, respiratory failure due to tumor compression, spinal cord compression), or deterioration of clinical status or eastern Cooperative oncology Group (eCoG) performance status, study treatment should be discontinued.
after up to 6 cycles of combination therapy, patients who have not experienced disease progression or discontinued blinded study treatment due to related toxicity will continue to receive assigned blinded maintenance with 3 mg/kg bavituximab or placebo monotherapy weekly until progression or toxicity. Laboratory assessments will be performed every 3 weeks. Radiographic tumor evaluations and exploratory biomarkers will be performed every 9 weeks until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons.
Patients who discontinue all study treatment but have not experienced disease progression or initiated
subsequent anticancer therapies will remain in the study and continue to undergo exploratory biomarkers and tumor assessments every
9 weeks until disease progression.
after patients have experienced disease progression or are no longer receiving any study treatment and have
initiated subsequent anticancer therapy, follow-up for survival (primary endpoint of the study) will begin.
Survival follow-up information will be collected at least every 3 months until death, loss to follow-up, or study
termination by the Sponsor.
in order to explore exposure-response relationships for safety and efficacy where possible and to assess the
effect of body size on bavituximab pharmacokinetics (PK) characteristics, PK sampling will be performed for
all treated patients. PK parameters will be estimated using population PK analyses, including covariate models
for intrinsic and extrinsic factors.
The following are requirements for entry into the study:
1. Written informed consent has been obtained prior to screening.
2. Male or female at least 18 years of age
3. Histologically or cytologically confirmed and documented stage IIIb/IV
non-squamous NSCLC according to the American Joint Committee on Cancer
Staging Manual (7th Edition) (confirmed by central review)
4. Radiographic disease recurrence or progression during or after front-line
platinum-based doublet chemotherapy treatment. Patients with known
EGFR-activating mutations or ALK translocations should have progressed after
appropriate targeted treatment (or did not tolerate appropriate targeted therapy).
5. ECOG performance status of 0 or 1
6. Adequate hematologic function (absolute neutrophil count [ANC] >= 1500 cells/[MICRO-SYMBOL]L;
hemoglobin >= 9 g/dL; platelets >= 100,000/[MICRO-SYMBOL]L
7. Adequate renal function (serum creatinine <= 1.5 mg/dL or calculated creatinine
clearance >= 60 mL/min using the Cockcroft-Gault equation)
8. Adequate hepatic function (total bilirubin <= upper limit of normal [ULN], serum albumin levels >= 3.0 g/dL, alanine aminotransferase [ALT] <= 1.5 x ULN and aspartate aminotransferase [AST] <= 1.5 x ULN). ALT and/or AST may be <= 5 x ULN if due to liver metastases.If ALT or AST is > 1.5 and <= 5 x ULN in patients with liver metastases, alkaline phosphatase must be <= 2.5 x ULN.
Patients with Gilbert[Single Quote]s syndrome are allowed if total bilirubin <= 2 x ULN and direct bilirubin is <= ULN.
9. Prothrombin time (PT) and/or international normalized ratio (INR) <= 1.5 x ULN and
activated partial thromboplastin time (aPTT) <= 1.5 x ULN if patient is not on anticoagulant therapy (a therapeutic PT and/or INR and aPTT is acceptable if the patient is on anticoagulants)
10. Female patients must have a negative serum human chorionic gonadotropin (hCG)
test within 1 week of Day 1 (pregnancy test not required for patients with bilateral
oophorectomy and/or hysterectomy or for those patients who are > 1 year
11. All patients of reproductive potential (ie, not surgically sterile or postmenopausal)must agree to use an effective method of contraception (˂1% failure rate per year) during and 3 months after end of study treatment (female) or during and 6 months after end of study treatment (male).