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Naiyer Rizvi



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      82TiP - IMpower030: Phase III study evaluating neoadjuvant treatment of resectable stage II-IIIB non-small cell lung cancer (NSCLC) with atezolizumab (atezo) + chemotherapy (ID 183)

      12:30 - 13:00  |  Author(s): Naiyer Rizvi

      • Abstract

      Background

      A standard of care for resectable early-stage NSCLC is surgery alone or in combination with adjuvant or neoadjuvant platinum-based doublet chemotherapy (PT-DC). Still, 30%-70% of patients develop recurrence and die from disease progression, highlighting the need for more effective treatments. Atezo, an anti–programmed death-ligand 1 (PD-L1) antibody that restores anti-tumour immunity, has shown promising efficacy as monotherapy and in combination with chemotherapy in advanced NSCLC. It is hypothesised that the combination of atezo and PT-DC may provide clinical benefit in the neoadjuvant setting by enhancing cancer cell killing and eradicating micrometastases, reducing the risk of disease recurrence. The objective of IMpower030 (NCT03456063) is to evaluate the efficacy and safety of atezo in combination with PT-DC as neoadjuvant treatment for patients with resectable early-stage NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Trial design

      IMpower030 is a global, Phase III, double-blind, randomized study in patients with histologically or cytologically confirmed, resectable stage II, IIIA, or select IIIB (T3N2) NSCLC (per AJCC/UICC, 8th ed). Study inclusion requires measurable disease per RECIST v1.1, ECOG PS of 0/1 and eligibility for R0 resection with curative intent and PT-DC. Patients who had received prior therapy for lung cancer or present with nonsquamous NSCLC with activating EGFR mutations or ALK translocation are excluded. Patients will be randomized to receive 4 cycles of neoadjuvant atezo (1200 mg Q3W, Arm A) or placebo (Arm B) in combination with an investigator-selected PT-DC regimen. Following unblinding, patients in Arm A will receive adjuvant atezo treatment for ≤ 16 cycles or until disease recurrence or unacceptable toxicity, and patients in Arm B will receive best supportive care and scheduled observational follow-up. Endpoints will include major pathological response (≤ 10% residual viable tumour tissue at time of resection), investigator-assessed event-free survival and disease-free survival per RECIST v1.1, OS, ORR, pathological complete response and patient-reported outcomes. Exploratory biomarkers will also be evaluated.

      d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification

      NCT03456063.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing assistance for this abstract was provided by Jessica Men, PharmD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      F. Hoffmann-La Roche, Ltd.

      213f68309caaa4ccc14d5f99789640ad Funding

      F. Hoffmann-La Roche, Ltd.

      682889d0a1d3b50267a69346a750433d Disclosure

      S. Peters: Ad board, honoraria: Daiichi, Debiopharm, FoundMed, Janssen, Merrimack, PharmaMar, Regeneron, Sanofi, Seattle Genetics; Ad boad, honoraria, talk: Lilly, Takeda; Talk, honoraria, investigation in trials: AZ, BI, BMS, Clovis; Ad board, honoraria, talk, investigation in trials: Roche, Merck, Novartis, Pfizer; Ad board, honoraria, investigation in trials: Illumina. A.W. Kim: Full-time employee: University of Southern California; Advisory board: Medtronic, Genentech; Other (support of parent study, funding of editorial support): F. Hoffmann-La Roche. B. Solomon: Support of parent study, funding of editorial support: Roche. D.R. Gandara: Research grants: AstraZeneca, Genentech, Novartis, Merck; Consultant/Advisory board: AstraZeneca, Celgene, CellMax, Genentech, Guardant Health, Inivata, IO Biotech, Lilly, Liquid Genomics, Merck, Samsumg Bioepis; Parent study, medical writing support: Roche. R. Dziadziuszko: Advisor/Board member: Roche, Novartis, Pfizer, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb; Speaker’s Bureau: Roche, Pfizer, Foundation Medicine; Support of parent study, funding of editorial support: Roche. A. Brunelli: Support of parent study, funding of editorial support: F. Hoffmann-La Roche. M.C. Garassino: Grants/research support: MSD, BMS, AZ, Roche, Celgene, Medimmune; Advisory board/Speakers’ bureau: MSD, BMS, AZ, Roche, Celgene, Medimmune, Incyte, Ignyta; Other (support of parent study, funding of editorial support): Roche. M. Reck: Speakers bureau, consulting, advisory role: Roche, Lilly, Pfizer, BI, AZ, MSD, BMS, Merck, Novartis, Celgene; Other (support of parent study, funding of editorial support): Roche. L. Wang, I. To, S.W. Sun, B.J. Gitlitz: Employee: Genentech; Other (support of parent study, funding of editorial support): Roche. A. Sandler: Employee: Genetech; Stock: Roche; Other (support of parent study, funding of editorial support): Roche. N. Rizvi: Consulting: AbbVie, AstraZeneca, BMS, EMD Sorono, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron; Advisory boards: Bellicum, Brooklyn Immunotherapeutics, Neogenomics, Gritstone; Equity: Bellicum, Brooklyn Immunotherapeutics, Gritstone, ARMO Board of Director (2017-2018) with Stock options vested with company acquisition by Lilly (June 25, 2018); Royalties: Personal Genome Diagnostics: Royalties related to patent filed by MSKCC, Determinants of cancer response to immunotherapy (PCT/US2015/062208); Research funding: BMS, Merck; Institutional financial interests: Clinical research: AstraZeneca, BMS, Genentech, GSK, Merck, Regeneron.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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    Proffered Paper session I (ID 57)

    • Event: ELCC 2019
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/10/2019, 16:30 - 18:15, Room C
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      LBA4 - Effect of post-study immunotherapy (IO) on overall survival (OS) outcome in patients with metastatic (m) NSCLC treated with first-line durvalumab (D) vs chemotherapy (CT) in the phase III MYSTIC study (ID 379)

      16:30 - 18:15  |  Author(s): Naiyer Rizvi

      • Abstract
      • Presentation
      • Slides

      Background

      In MYSTIC (NCT02453282), an open-label, Phase 3 study of first-line D (anti-PD-L1) ± tremelimumab vs platinum-based CT in mNSCLC, while not statistically significant, a clinically meaningful improvement in OS was seen with D vs CT in pts with tumour cell PD-L1 expression ≥25% (PD-L1 TC ≥25%; HR 0.76 [97.54% CI 0.56–1.02], p=0.036). Here we describe subsequent treatment patterns and explore the effect of subsequent IO on the OS outcome with D vs CT.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      IO/CT-naïve mNSCLC pts were randomised to D (20 mg/kg i.v. q4w until disease progression) or CT (up to 6 cycles; pemetrexed maintenance permitted). In-study crossover from CT to D was not allowed. For D vs CT, the primary endpoint was OS in pts with PD-L1 TC ≥25%. Three statistical models were employed in exploratory analyses to evaluate the effect of subsequent (post-study) IO on the OS data: the rank preserving structural failure time (RPSFT) method, the inverse probability of censoring weighting (IPCW) method, and a 2-stage method.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      163 and 162 pts with PD-L1 TC ≥25% were randomised to D and CT, respectively. At data cut-off (04 Oct 2018), 44.8% of pts in the D arm and 58.6% of pts in the CT arm had received subsequent treatment (Table). Most pts started subsequent treatment within 2 mos of discontinuing study treatment. Among pts who received subsequent treatment, IO was administered to 10/73 (13.7%) pts in the D arm and 64/95 (67.4%) pts in the CT arm; most commonly nivolumab. Using the 2-stage method, which was the most appropriate for evaluating the effect of subsequent IO, OS was improved with D vs CT (HR 0.66 [95% CI 0.51, 0.86]).

      Durvalumab (n=163)Chemotherapy (n=162)
      Pts who received study treatment, n (%)161 (98.8)153 (94.4)
      →Pts who discontinued study treatment136 (83.4)152 (93.8)
      →Pts remaining on study treatment25 (15.3)1 (0.6)
      Pts who received any subsequent treatment, n (%)73 (44.8)95 (58.6)
      →Immunotherapy10 (6.1)64 (39.5)
      →→Nivolumab3 (1.8)50 (30.9)
      →→Pembrolizumab4 (2.5)11 (6.8)
      →→Atezolizumab2 (1.2)3 (1.9)
      →→Durvalumab02 (1.2)
      →→Tremelimumab01 (0.6)
      →→Other immunotherapy1 (0.6)2 (1.2)
      →Cytotoxic chemotherapy70 (42.9)58 (35.8)
      →Other systemic therapies*18 (11.0)18 (11.1)

      Denominators for percentages are the number of pts randomised.

      Excluding immunotherapy and cytotoxic chemotherapy.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      In the MYSTIC study, a markedly higher proportion of pts in the CT arm than in the D arm received subsequent IO, which may have confounded the primary OS outcome. An exploratory analysis showed increased OS benefit with first-line D vs CT after adjusting for the effect of subsequent IO.

      b651e8a99c4375feb982b7c2cad376e9 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Samantha Holmes, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca PLC.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      N. Reinmuth: Personal fees: BMS, Roche, AstraZeneca, Takeda, Novartis, Boehringer Ingelheim, MSD, Lilly, outside the conduct of the study. B.C. Cho: Grants/research support: Novartis, AstraZeneca, Yuhan, ONO/BMS, MSD, Bayer; Advisor/honoraria fees: AstraZeneca, Roche, Boehringer Ingelheim, Yuhan, BMS, MSD, Novartis; Speaker’s bureau fees: AZ, BMS, MSD, Novartis. J. Schneider: Stock/other ownership: AstraZeneca, Bristol-Myers Squibb, Pfizer, Celgene, Loxo; Consulting/advisory role: Takeda Oncology; Research funding: AstraZeneca, Bristol-Myers Squibb. F.A. Shepherd: Consultancy/advisory role: Lilly, AstraZeneca, Boehringer Ingelheim, Merck Serono; Stock ownership: Lilly, AstraZeneca; Honoraria: Lilly, AstraZeneca, BMS, Roche/Genentech, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim; Research funding: Lilly, Pfizer, BMS, AstraZeneca, Roche Canada, Merrimack. S. Peters: Personal fees: AbbVie, Amgen, AZ, Bayer, Biocartis, BI, BMS, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda; Non-financial support: Amgen, AZ, BI, BMS, Clovis, F. Hoffmann-La Roche, Illumina, MSD, Merck Serono, Novartis, Pfizer. S.L. Geater: Research grants/funding: AstraZeneca, Roche, Novartis. T. Van Ngoc: Research funding: AstraZeneca, GSK, Novartis. M.C. Garassino: Personal fees: Eli Lilly, Boehringer Ingelheim, Otsuka Pharma, AstraZeneca, Novartis, BMS, Roche, Pfizer, Celgene, Incyte, Inivata, Takeda, Tiziana Science, Clovis, Merck Serono, Bayer, MSD, GSK. F. Liu, D. Clemett, P. Thiyagarajah, M. Ouwens, U. Scheuring: Full-time employment: AstraZeneca. N. Rizvi: Advisory boards: AbbVie, AZ, BMS, EMD Serono, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Neogenomics, Oncomed, Gritstone, Bellicum; Equity: Oncomed, Gritstone, Bellicum, ARMO; Royalties: PGDX (patent filed by MSKCC). All other authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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