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B. Liu

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    ORAL 02 - PD1 Axis Immunotherapy 2 (ID 87)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      ORAL02.07 - Atezolizumab (MPDL3280A) Combined with Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer (NSCLC): A Phase Ib Safety and Efficacy Update (ID 2208)

      10:45 - 12:15  |  Author(s): B. Liu

      • Abstract
      • Presentation
      • Slides

      Despite advances in treatment for NSCLC, the standard first-line treatment for metastatic disease remains platinum-based doublet chemotherapy with historical overall response rates (ORRs) of ≈30%. Preclinical data suggest that chemotherapy treatment can result in antigen release in the tumor microenvironment, potentially enhancing effects of cancer immunotherapy. Atezolizumab (MPDL3280A) is a human monoclonal antibody that targets the PD-L1/PD-1 immune checkpoint, while leaving the PD-L2/B7.1 interaction intact (which may reduce the risk of autoimmune lung toxicity). As atezolizumab has shown promising activity in advanced NSCLC, we investigated atezolizumab in combination with chemotherapy.

      A Phase Ib study was conducted to evaluate atezolizumab with chemotherapy in locally advanced or metastatic NSCLC patients who had not received chemotherapy for advanced disease. Pts received atezolizumab 15 mg/kg IV q3w with standard chemotherapy (carboplatin plus either paclitaxel [Arm C], pemetrexed [Arm D; nonsquamous] or weekly nab-paclitaxel [Arm E]) for 4-6 cycles followed by atezolizumab maintenance until progression. RECIST v1.1 was used to assess ORRs (unconfirmed) in pts dosed by Jun 29, 2014 (data cutoff: Sep 29, 2014). PD-L1 expression was centrally evaluated using the SP142 IHC antibody assay.

      37 NSCLC pts were safety evaluable (8 in Arm C; 14 in Arm D; 15 in Arm E). Across these arms, 54% of pts were male, with a median age of 65 y (range, 40-82 y). 81% had non-squamous NSCLC, and 19% had squamous NSCLC. Median safety follow-up was 22.0 wks (range, 0.1-49.4 wks). Across arms, all-Grade AEs regardless of attribution included those commonly associated with chemotherapy, such as nausea (Arms C & D, 50%; Arm E, 73%), fatigue (Arm C, 38%; Arm D, 36%; Arm E, 73%) and constipation (Arm C, 25%; Arm D, 71%; Arm E, 27%). The most common Grade 3-4 atezolizumab-related AEs included anemia (Arms D & E, 7%), neutropenia (Arm C, 13%; Arm D, 7%) and thrombocytopenia (Arms D & E, 7%), with no pneumonitis or autoimmune renal toxicity observed. One potentially atezolizumab-related Grade 5 AE was observed in Arm D (candidemia after prolonged neutropenia). 30 pts were efficacy evaluable, and responses were observed in all arms regardless of PD-L1 expression (Table). Updated clinical data will be presented.

      Table. RECIST v1.1 Responses in Patients with NSCLC
      Arm C: carboplatin + paclitaxel (n = 5) Arm D: carboplatin + pemetrexed (n = 12) Arm E: carboplatin + nab-paclitaxel (n = 13) All Indicated Arms (n = 30)
      ORR, % 60% 75% 62% 67%
      95% CI, % 19%-92% 45%-93% 33%-83% 48%-82%
      CR, n 0 0 2 2
      PR, n 3 9 6 18

      Atezolizumab plus standard first-line chemotherapy was well tolerated in advanced NSCLC pts, with no unexpected toxicities. Clinical activity was promising and supportive of a potential synergy of atezolizumab with chemotherapy. Based on these results, several Phase III studies have been initiated.

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