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Sang-We Kim



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    Proffered Paper session III (ID 64)

    • Event: ELCC 2019
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/12/2019, 08:30 - 10:00, Room A
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      84O - Phase I study of gefitinib (G) + durvalumab (D) for locally advanced/metastatic non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) sensitising mutations (ID 180)

      08:30 - 10:00  |  Author(s): Sang-We Kim

      • Abstract
      • Presentation
      • Slides

      Background

      G and D have both shown efficacy in patients (pts) with NSCLC; G + D may improve durability of response.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      This Phase 1 dose escalation (Part A) and expansion (Part B) study (NCT0208811) assessed G 250 mg once daily + D 3 mg/kg (Part A) or 10 mg/kg (Parts A + B) every 2 weeks in pts with locally advanced/metastatic NSCLC. Part A pts were all comers who had failed to respond/relapsed following standard treatment (Tx). Part B pts had sensitising EGFR mutations and were tyrosine kinase inhibitor naïve: Arms 1 + 1a received G + D; Arm 2 received G (4 weeks) before G + D. Primary objective: safety/tolerability. Secondary objectives: pharmacokinetics (PK), pharmacodynamics, immunogenicity (anti-drug antibodies [ADAs]) and efficacy. Exploratory objective: evaluation of biomarkers (e.g. tumour programmed cell death ligand-1 [PD-L1]) and relationship with efficacy.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      There were no dose limiting toxicities in Part A (n = 16) and D 10 mg/kg was used in Part B. In Part B (n = 40) all pts had possible Tx related adverse events (TRAEs; Table): diarrhoea (68%) and elevated alanine aminotransferase (ALT; 58%) were the most common TRAEs; elevated ALT (20%) and aspartate aminotransferase (15%) were the most common TRAEs leading to discontinuation. PK were as expected, inhibition of soluble PD-L1 was observed in all pts and no Tx emergent ADAs were observed. In Arms 1 + 1a, most patients achieved objective response (63.3%; 95% confidence intervals [CI]: 43.9, 80.1), median duration of response was 9.2 months (95% CI: 3.7, 14.0) and median progression-free survival (mPFS) was 10.1 months (95% CI: 5.5, 15.2; Table). PD-L1 expression ≥20% was associated with numerical improvements in mPFS (Table).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      G + D had a high discontinuation rate due to liver related TRAEs and there was no additional benefit vs historical data for G alone. However, tumours expressing PD-L1 had favourable PFS and could be investigated further.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02088112; March 14, 2014.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing support, under the direction of the authors, was provided by Lauren McNally, MSci, of CMC CONNECT, a division of McCann Health Medical Communications Ltd, Glasgow, UK, with funding from AstraZeneca PLC, in accordance with Good Publication Practice (GPP3) guidelines.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      MedImmune LLC (a wholly owned subsidiary of AstraZeneca PLC).

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca PLC.

      682889d0a1d3b50267a69346a750433d Disclosure

      T. Yeh, W. Tang, M. Tang, H.K. Angell, M.P. Roudier, M. Marotti: Employee: AstraZeneca. R. Taylor: Employee, contractor: AstraZeneca. D.L. Gibbons: Advisory boards/research funding: AstraZeneca. All other authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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