Study of TRC105 + Paclitaxel/Carboplatin and Bevacizumab in Patients With NSCLC

Phase 1

Completed

Brief Summary: This is a single center, open-label, nonrandomized, phase 1b, dose-finding study of TRC105 in combination with standard dose bevacizumab and paclitaxel/carboplatin in treatment-naive patients with stage IV non-squamous NSCLC.

Detailed Description: Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in non-squamous non-small cell lung cancer (NSCLC) patients when given with carboplatin and paclitaxel. TRC105 is an antibody to endoglin, an essential angiogenic target expressed on proliferating endothelial cells that is distinct from the VEGFR and overexpressed in response to VEGF inhibition. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of antibodies and small molecules that target the VEGFR. In a phase 1b study, the combination of TRC105 and bevacizumab produced radiographic reductions in tumor volume in bevacizumab-refractory patients, and was well tolerated. TRC105 was also well tolerated with chemotherapy in a trial with capecitabine in breast cancer patients. The use of TRC105 with bevacizumab and paclitaxel/carboplatin may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with bevacizumab and paclitaxel/carboplatin alone.

Recruitment & Eligibility

Inclusion Criteria

Stage 4 Non-Squamous Cell Lung Cancer that has not been treated previously with systemic chemotherapy or bevacizumab, but may have received prior targeted treatment (e.g., alk1 inhibitor)
ECOG performance status ≤ 1
Measurable disease by RECIST

Key

Exclusion Criteria

Non-small cell lung cancer of squamous histology
Current treatment on another therapeutic clinical trial
Patients who have received wide field radiotherapy ≤ 28 days (defined as > 50% of volume of pelvic bones or equivalent) or limited field radiation for palliation < 14 days prior to study registration or those patients who have not recovered adequately from side effects of such therapy
Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia). Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.

Arm && Interventions

Group	Intervention	Description
TRC105 + B + P + C	TRC105	TRC105 in combination with standard dose bevacizumab and paclitaxel/carboplatin in treatment-naive patients with stage IV non-squamous NSCLC.

Primary Outcome Measures

Name	Time	Method
Treatment-Emergent Adverse Events	from screening until completion of follow-up, on average 6 months	Incidence of treatment-emergent (i.e. TRC105, bevacizumab, paclitaxel and/or carboplatin) adverse events by CTCAE v4.03

Secondary Outcome Measures

Name	Time	Method
Overall RECIST 1.1 Response Rate	6 months	Response rate determined according to RECIST 1.1 criteria
Percent of Patients With Progression-free Survival (PFS) at 6 Months	6 months	Number of patients with progression-free survival at 6 months determined according to RECIST 1.1 criteria
Number of Patients Who Have TRC105 Positive Anti-Product Antibodies	6 months	Anti-product antibody concentrations will be measured using validated ELISA methods. Anti-product antibody concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles.
Median Progression Free Survival	months	Median duration of progression free survival according to RECIST 1.1 criteria
Pharmacokinetic Profile of TRC105 When Given With Bevacizumab and Paclitaxel/Carboplatin	3 months	Trough serum TRC105 pharmacokinetic concentrations at steady state (cycle 3 day 1) will be measured using validated ELISA methods.