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J. Keef
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-022 - A Phase 1B Study of TRC105 in Combination with Paclitaxel/Carboplatin and Bevacizumab in Patients with Stage 4 Non-Squamous Cell Lung Cancer (ID 8262)
09:30 - 09:30 | Author(s): J. Keef
- Abstract
Background:
Given the modest/transitory benefit of bevacizumab(B)/chemotherapy(CT) in advanced non-small cell lung cancer (NSCLC) and the tendency of tumors to develop escape pathways of angiogenesis,investigation of dual anti-angiogenic therapy may result in more effective angiogenesis inhibition. TRC105 is an antibody to endoglin,an essential angiogenic target expressed on proliferating endothelial cells,and overexpresed in response to VEFG inhibition.This phase 1b study of TRC105 in combination with standard (STD) dose of B with paclitaxel/carboplatin(P/Crb) in advanced non-squamous (NSQ) NSCLC had the primary objectives of safety/tolerability and to determine a recommended phase 2 dose.Secondary objectives included preliminary evidence of antitumor activity and pharmacokinetic(Pks) profile of TRC105.
Method:
A dose finding study (3+3 design) of TRC105 with B(15mg/kg), P(200mg/m2),and Crb(AUC6), given iv on day 1 of each 21 day cycle.Two dose levels of TRC105 were evaluated: 8mg/kg (cohort 1) and 10mg/kg (cohort 2), administered iv weekly. An expanded cohort at dose level 2 is being evaluated. A maintenance phase with TRC105 + B was considered after of induction therapy in those pts without evidence of progressive disease. Safety and efficacy assessments were determined by the NCI-CTCAE (v 4),and RECIST 1.1,respectively. Eligible pts had PS 0-1, chemotherapy naive stage 4 NSQ-NSCLC,measurable disease, and no significant cardiovascular comorbidities. Pts with asymptomatic treated CNS metastases were allowed.Other parameters assessed included Pks,immunogenicity,and angiogenic biomarkers in plasma.Descriptive statistics were used to summarize pt characteristics, safety, efficacy, Pks and biomarkers.
Result:
Overall safety population comprised 9 pts receiving ≥ 1 cycle of treatment . Median age was 65 years, 55% were women, and one pt had brain metastases. A total of 67 cycles of treatment were delivered (median of 8 cycles). The most frequent grade (G) 3 adverse events:anemia (55%),fatigue (55%),,and neuropathy (44%).There was a G3 epistaxis and a G5 neutropenic event. Responses shown below: Figure 1
Conclusion:
TRC105 with STD CT was associated with an acceptable safety profile.
