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Martin Smoragiewicz



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    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      MA11.04 - Platinum Doublet + Durvalumab +/- Tremelimumab in Patients with Advanced NSCLC: A CCTG Phase IB Study - IND.226 (Now Available) (ID 927)

      14:00 - 15:30  |  Author(s): Martin Smoragiewicz

      • Abstract
      • Presentation
      • Slides

      Background

      Studies of single agent immune checkpoint inhibitors with platinum-based chemotherapy in non-small cell lung cancer (NSCLC) have demonstrated survival benefit over chemotherapy alone. The primary objective of this multi-centre study was to evaluate the safety and tolerability of durvalumab (Du), a PD-L1 inhibitor, +/- tremelimumab (Tr), a CTLA-4 inhibitor, with one of four standard platinum-doublet regimens (pemetrexed (pem), gemcitabine, etoposide (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)), in order to establish a recommended phase II dose (R2PD) for each combination. This abstract updates the results in the NSCLC cohort in this study.

      Method

      Patients (pts), regardless of tumour PD-L1 status, were enrolled into one of six dose levels (Table 1). Dose escalation was according to a Rolling Six type design. Concurrent enrollment of cohorts was allowed. ind 226 abstract wclc methods.png

      Result

      Seventy-three pts (median age=63 (range 34-80); 52% female; 77% non-squamous) were enrolled. The majority of drug-related adverse events (AEs) were grade 1 or 2. Most AEs were related to chemotherapy; other AEs were chemotherapy or immune-related (renal, hepatic, skin and pulmonary toxicity). AEs that were considered related to Du or Tr (immune related AEs (irAEs)) were mainly grade 1 or 2. The most common irAEs were fatigue (64%), rash/itch (42%), diarrhea/colitis (34%), anorexia (22%), thyroid dysfunction (19%), and nausea/vomiting (21/12%). The most common grade 3 or 4 irAEs were diarrhea/colitis (11%), fatigue (10%), and rash (5%). No treatment related grade 5 toxicities were reported. Twenty pts (27%) discontinued treatment due to an AE. Twelve pts (16%) discontinued treatment for toxicity related to D+/-T. Objective response rate (ORR) was 50.7% (95% CI = 38.7-62.6%). Median progression free survival (mPFS) was 6.5 months (95% CI = 5.5-9.4). Median overall survival (mOS) was 19.8 months (95% CI = 14.8-not yet reached). ORR was similar for all levels of PD-L1 staining including PD-L1 negative patients. ORR for pts with EGFR mutations (N=5) was similar to the ORR of wild type pts. Exploratory analyses suggest mPFS and mOS were longer in patients who experienced irAEs.

      Conclusion

      In this PD-L1 unselected patient population, Du and Tr can be safely combined with full doses of platinum-doublet chemotherapy. The ORR, mPFS and mOS are similar to results reported from other immunotherapy + chemotherapy combination trials. A randomized trial, CCTG BR.34, is evaluating the incremental benefit of adding platinum doublet to Du+Tr.

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