Non-Squamous Non-Small Cell Lung Cancer
Conditions
Brief summary
This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with paclitaxel plus platinum in patients with incurable Stage IIIB or Stage IV squamous non-small cell lung cancer (NSCLC). Patients will be randomized to receive either onartuzumab (MetMAb) 15 mg/kg iv or placebo on Day 1 of each 21-day cycle in combination with 4 cycles of paclitaxel 200 mg/m2 iv and platinum (carboplatin/cisplatin) iv on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will continue with either onartuzumab (MetMAb) or placebo as maintenance therapy until disease progression or unacceptable toxicity occurs.
Interventions
DRUGPlacebo
Matching onartuzumab (MetMAb) placebo iv, Day 1 of each 21-day cycle
standard dose iv, Day 1 of each 21-day cycle, 4 cycles
DRUGonartuzumab
15 mg/kg iv, Day 1 of each 21-day cycle
DRUGpaclitaxel
200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/= 18 years of age * Histologically or cytologically confirmed Stage III B or Stage IV squamous non-small cell lung cancer (NSCLC) * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * No prior chemotherapy for squamous NSCLC * Adequate tissue for central IHC assay of Met receptor, and EGFR testing if EGFR status is unknown * Radiographic evidence of disease
Exclusion criteria
* Prior systemic treatment for Stage IIIB or IV squamous NSCLC * NSCLC with histology classified as adenocarcinoma, large cell, mixed adenosquamous, or NSCLC not otherwise specified (NOS) * Prior exposure to experimental treatment targeting either the HGF or Met pathway * Patients with tumors confirmed to have EGFR-activating mutations who are suitable for anti-EGFR therapy (e.g. gefitinib or erlotinib), as determined by the investigator * Uncontrolled brain metastases and treatment by neurosurgical resection or brain biopsy within 4 weeks prior to Day 1 of Cycle 1 * History of another malignancy in the previous 3 years except for prior history of in situ cancer or basal or squamous cell skin cancer * Pregnant or lactating women * Uncontrolled diabetes * Impaired bone marrow, liver or renal function as defined by protocol * Significant history of cardiovascular disease * Positive for HIV infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival (tumor assessments according to RECIST criteria) | up to approximately 32 months |
| Progression-free survival: Subgroup of patients with Met diagnostic-positive squamous NSCLC | up to approximately 32 months |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response (time from first documented objective response to disease progression) | up to approximately 32 months |
| Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks) | up to approximately 32 months |
| Safety: Incidence of adverse events | up to approximately 32 months |
| Overall survival | up to approximately 32 months |
| Plasma concentrations of paclitaxel/platinum | Pre- and post-dose on Day 1 of Cycles 1 and 4 |
| Serum levels of anti-therapeutic antibodies (MetMAb ATAs) | Pre-dose Day 1 of Cycles 1, 2 and 4 |
| Pharmacokinetics: serum concentration (Cmin/Cmax) | Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and up to 2 years |
| Overall response rate (tumor assessments according to RECIST criteria) | up to approximately 32 months |
Countries
Argentina, France, Germany, Israel, Italy, Latvia, Spain, United Kingdom, United States
Outcome results
None listed