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Bonne Adams



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-87 - A Phase 1b Study of TRC105 In Combination with Paclitaxel/Carboplatin and Bevacizumab in Patients with Stage 4 Non-Squamous Cell Lung Cancer  (ID 12978)

      16:45 - 18:00  |  Author(s): Bonne Adams

      • Abstract
      • Slides

      Background

      Endoglin plays a critical role in angiogenesis and is implicated in resistance to VEGF inhibition. TRC105, an endoglin antibody, has been shown to potentiate the anti-angiogenic effect of bevacizumab (B) in pre-clinical models of human angiogenesis. Given the critical role of anti-angiogenic therapy in the treatment of advanced NSCLC and the tendency of the tumor to develop escape pathways of angiogenesis following treatment with anti-VEGF agent, investigation of dual anti-angiogenic therapy in advanced NSCLC is indicated.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A standard (3+3) dose-escalation design of TRC105 with15 mg/kg bevacizumab (B), 200 mg/m2 paclitaxel (P) and 6 AUC carboplatin (C) given IV on day 1 of each 21-day cycle was employed, followed by an expanded cohort to further assess the safety and tolerability of the recommended phase 2 dose (RPTD) of TRC105. Patients completed induction therapy with TRC105 + B, P and C for a maximum of 6 cycles with those demonstrating no evidence of disease progression transitioned to a maintenance phase of TRC105 + B. Secondary endpoints: ORR, PFS, OS, PK, immunogenicity and angiogenic biomarkers. Key inclusion criteria: chemotherapy-naïve stage 4 NSQ-NSCLC, ECOG < 1, measurable disease and no significant cardiovascular comorbidities.

      4c3880bb027f159e801041b1021e88e8 Result

      Fifteen pts have been enrolled; three were unevaluable for efficacy due to DLT of Grade 3 rash and unrelated SAE’s of Grade 3 weakness and Grade 3 hypoxia. Four of 12 evaluable pts achieved PR, one with 81% tumor reduction. Median PFS was 6.54 months. Common adverse events regardless of relationship included epistaxis, fatigue, telangiectasia, diarrhea, headache and nausea. Common TRC105 related AEs included epistaxis, telangiectasia, fatigue and headache. One patient experienced Grade 5 neutropenic sepsis considered unrelated to TRC105 or B. Analysis of the angiogenic biomarkers will be presented.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Induction treatment for six 3-week cycles withTRC105 + B, P, and C, followed by maintenance therapy with TRC105 + B until disease progression was tolerable and did not potentiate the toxicity of B, P or C. The combination of TRC105 + B, P and C demonstrated signs of activity including PR in 4 of 12 evaluable pts.

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