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C. Theuer
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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): C. Theuer
- 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.
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P1.04 - Clinical Design, Statistics and Clinical Trials (ID 690)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.04-012 - A Phase 1b Dose-Escalation Study of TRC105 in Combination with Nivolumab in Patients with Metastatic Non-Small Cell Lung Cancer (ID 8386)
09:30 - 09:30 | Author(s): C. Theuer
- Abstract
Background:
Nivolumab (N) has demonstrated clinical benefit in advanced non-small cell lung cancer (NSCLC) patients (PTS) who have progressed to platinum-based chemotherapy: improved overall survival (OS) versus (Vs) docetaxel in squamous NSCLC (median OS of 9.2 months [mo} Vs 6 mo) and in non-squamous NSCLC (median OS of 12.2 mo Vs 9.4 mo). TRC105 is an antibody to endoglin, a receptor expressed on proliferating endothelial cells and myeloid derived suppressor cell (MDSCs). MDSCs also inhibit anti-cancer immunity, but by a mechanism of action that is distinct from that inhibited by N. TRC105 inhibits tumor growth in preclinical models and complements the activity of antibodies that target the programmed death receptor (PD-1). Its toxicity profile is distinct from that of N. By targeting MDSCs, TRC105 has the potential to complement N and improve clinical efficacy over that seen with single agent N.
Method:
This is a phase 1b,dose-finding (3+3 design) study of TRC105 in combination with standard dose (240mg) of N in pts with advanced NSCLC with disease progression to platinum-containig doublet chemotherapy.The primary objective is to evaluate safety and tolerability and determine a recommended phase 2 dose of TRC105 in combination with standard dose of N. Secondary objectives include: preliminary evidence of antitumor activity by assessing response rate and progression-free survival; characterize the pharmacokinetic profile of TRC105 when given in combination with N; and to explore biologic effects of TRC105 and N on circulating immune cells. Two dose levels of TRC105 are initially considered: Dose Level I: 8mg/kg intravenously (IV) weekly for 4 weeks → 15mg/kg every 2 weeks; Level II: 10mg/kg (iv) for 4 weeks → 15mg/kg every 2 weeks. N will be administered IV every 2 weeks in both cohorts of pts.Toxicity and efficacy assessments will be determine using NCI-CTCAE(V 4) and RECIST (V 1.1),respectively. The dose-limiting toxicity (DLT) evaluation period will be the first 4 weeks of the first cycle of treatment. It is anticipated that up to 18 pts will be enrolled in the study,and up to 12 pts at the maximum tolerated dose(MTD).. Main criteria for inclusion are: confirmed stage 4 NSCLC,prior platinum-based doublets,measurable disease,ECOG PS 0-1,PD-L1 expression >/ 1%,adequate organ function,and no prior therapy with an immuno check point inhibitor. Descriptive statistics will be used to summarize pt characteristics,safety/efficacy/pharmacokinetic parameters ,and immunologic biomarkers.
Result:
Section not applicable
Conclusion:
Section not applicable
