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S.N. Gettinger



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    Immunotherapies and targeted therapies in advanced NSCLC (ID 39)

    • Event: ELCC 2017
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
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      84O - Atezolizumab as first-line (1L) therapy for advanced non-small cell lung cancer (NSCLC) in PD-L1–selected patients: Efficacy data from the BIRCH trial (ID 367)

      14:45 - 16:15  |  Author(s): S.N. Gettinger

      • Abstract
      • Slides

      Background:
      Atezolizumab (atezo) inhibits binding of PD-L1 to its receptors, PD-1 and B7.1, restoring tumor-specific T-cell immunity and leaving the PD-L2/PD-1 interaction intact. This single-arm Phase II study (BIRCH; NCT02031458) was designed to evaluate atezo monotherapy in PD-L1–selected patients with advanced NSCLC. A previous analysis (median follow-up, 8.5 months) demonstrated clinical activity in chemotherapy-naive 1L and 2L+ PD-L1–selected patients. Here we present updated efficacy data for 1L patients.

      Methods:
      Eligible patients had PD-L1–selected advanced-stage NSCLC, with no prior chemotherapy or CNS metastases. PD-L1 was centrally evaluated using the VENTANA SP142 IHC assay. Enrolled patients expressed PD-L1 on ≥ 5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), ie, TC2/3 or IC2/3. Those with EGFR mutation or ALK rearrangement must have had prior treatment with an appropriate TKI. Atezo was administered (1200 mg IV q3w) until radiographic disease progression or unacceptable toxicity. The primary endpoint was independent review facility (IRF)–assessed ORR; secondary endpoints included investigator (INV)-assessed ORR, DOR, PFS (RECIST v1.1) and OS.

      Results:
      With a median duration of survival follow-up of 22.5 months, INV-assessed ORR was 25% in TC2/3 or IC2/3 (all treated) patients and 34% in TC3 or IC3 patients (Table). Median OS was 23.5 months in all treated patients and 26.9 months in the TC3 or IC3 subgroup. Responses were observed in both EGFR and KRAS mutant and wild-type tumors. The safety profile was consistent with previous atezo NSCLC studies.

      Conclusions:
      With a median follow-up of 22.5 months, atezo continued to demonstrate durable clinical benefit in 1L NSCLC, in both EGFR and KRAS mutant and wild-type tumors. These results support ongoing Phase III trials evaluating atezo vs chemotherapy in 1L NSCLC.rnTable: 84Orn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
      Endpoint (95% CI)TC3 or IC3[a] (n = 65)TC2/3 or IC2/3[b] (n = 138)
      INV ORR, %34%25%
      (22.6-46.7)(18.4-33.5)
      EGFR mutant/wild type, ORR, %25%/31%31%/22%
      KRAS mutant/wild type, ORR, %38%/30%31%/22%
      Median DOR, moNE16.5
      (8.5-NE)(9.9-NE)
      Median OS, mo26.923.5
      (12.0-NE)(18.1-NE)
      12-mo OS rate, %61.5%66.4%
      (49.0-74.0)(58.1-74.6)
      Median PFS, mo7.37.3
      (4.9-12.0)(5.7-9.7)
      12-mo PFS rate, %36.5%32.5%
      (24.0-48.9)(24.2-40.8)
      rnNE, not estimable.rnaTC ≥ 50% or IC ≥ 10% PD-L1–expressing cells.rnbTC or IC ≥ 5% PD-L1–expressing cells.rn

      Clinical trial identification:
      NCT02031458

      Legal entity responsible for the study:
      F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

      Funding:
      F. Hoffmann-La Roche Ltd/Genentech Inc, a member of the Roche Group

      Disclosure:
      M.C. Garassino: Honoraria, Consulting, Speaker\'s Bureau, research funding, expert testimony, travel expenses: MSD, BMS, AZ, Lilly, Roche. D. Christoph: Honoraria, Speaker\'s Bureau: BI, BMS, Chugai, Novartis, Merck, MSD, Pfizer, Roche; Consulting: BI, BMS, Novartis, Pfizer, Roche; Expert testimony: BI, BMS, Novartis, Pfizer, Roche. J. Chaft: Advisor for Genentech and Astra Zeneca. M.L. Johnson: Consulting: Genentech, Celgene, BI; Research funding: OncoMed, BerGenBio, Lilly, EMD Serono, Kadmon, Janssen, Mirati, Genmab, Pfizer, AZ, Roche/Genentech, Stemcentrix, Novartis, Checkpoint, Array, Regeneron. S. Mocci: Employee, stock: Roche/Genentech. S.N. Gettinger: Consulting: BMS; Research funding: Roche/Genentech, BMS, ARIAD, Incyte, Celldex. E. Felip: Advisory Boards: Lilly, Pfizer, BI, MSD, Roche; Speaker\'s Bureau: AZ, BMS, Novartis. All other authors have declared no conflicts of interest.

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    Targeted therapies and management of brain metastasis (ID 40)

    • Event: ELCC 2017
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
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      87O - Brigatinib in ALK+ NSCLC pts with intracranial CNS metastases in 2 clinical trials (ID 241)

      16:45 - 18:15  |  Author(s): S.N. Gettinger

      • Abstract
      • Presentation
      • Slides

      Background:
      The investigational next-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib is being evaluated in patients (pts) with ALK-positive non–small cell lung cancer (ALK+ NSCLC) in a phase 1/2 trial (Ph1/2) and a pivotal phase 2 trial (ALTA); most of these pts had intracranial central nervous system (CNS) metastases at baseline.

      Methods:
      In Ph1/2 (NCT01449461), pts with advanced malignancies, including ALK+ NSCLC, received brigatinib (30–300 mg/d). In ALTA (NCT02094573), crizotinib-resistant pts with advanced ALK+ NSCLC received brigatinib at 90 mg qd in arm A or 180 mg qd with a 7-day lead-in at 90 mg in arm B. ALK+ NSCLC pts with baseline brain metastases were analyzed. CNS efficacy in both trials and safety in ALTA are shown.

      Results:
      In Ph1/2 and ALTA, 50/79 (63%) and 154/222 (69%) ALK+ NSCLC pts had baseline brain metastases based on independent review committee (IRC) and investigator assessment, respectively. Most pts had received chemotherapy (Table). In Ph1/2, 25/50 (50%) pts were receiving brigatinib as of 16 November 2015; in ALTA, 101/154 (66%) pts were receiving brigatinib as of 29 February 2016. In pts with measurable brain lesions, confirmed intracranial objective response rate was 53% in Ph1/2 and 42%/67% in ALTA A/B (Table). In pts with only nonmeasurable brain lesions, 35% (11/31) in Ph1/2 and 7% (4/54)/18% (10/55) in ALTA A/B had confirmed complete resolution of brain lesions. Further data are shown in the table. The most common treatment-emergent adverse events (TEAEs) in the 151 treated ALTA pts with baseline brain metastases were nausea (A/B, 32%/43%), headache (30%/30%), diarrhea (18%/36%), cough (21%/30%), and vomiting (25%/26%); the most common grade ≥3 TEAEs were increased blood creatine phosphokinase (1%/11%), hypertension (4%/7%), increased lipase (3%/3%), and pneumonia (1%/4%).

      Conclusions:
      Brigatinib yielded substantial clinical activity in ALK+ NSCLC pts with brain metastases in 2 trials.rnTable: 87OBaseline characteristics and IRC-assessed intracranial efficacy of brigatinib in ALK+ NSCLC Pts with brain metastases at baselinern

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
      rnPh1/2 n = 50ALTA Arm A n = 80ALTA Arm B n = 74
      Median age, years534955
      Received prior chemotherapy, %767476
      Crizotinib-naive, %800
      Pts evaluable for intracranial efficacy by IRC, n[a]468073
      Median iPFS, months14.615.612.8
      Pts with measurable brain lesions, n152618
      iORR, n (%)8 (53)11 (42)12 (67)
      iDCR, n (%)13 (87)22 (85)15 (83)
      No rad/active[b] subset, n91915
      iORR, n (%)6 (67)8 (42)11 (73)
      iDCR, n (%)8 (89)16 (84)14 (93)
      rniDCR = intracranial disease control rate, iORR = intracranial objective response rate (confirmed), iPFS = intracranial progression-free survivalrnaLast scan date: 8 October 2015 in Ph1/2; 14 April 2016 in ALTArnbNo prior brain radiotherapy in Ph1/2; active (untreated or treated and progressed) brain lesions in ALTArn

      Clinical trial identification:
      NCT01449461 and NCT02094573

      Legal entity responsible for the study:
      ARIAD Pharmaceuticals, Inc.

      Funding:
      ARIAD Pharmaceuticals, Inc.

      Disclosure:
      M. Tiseo: Consulting or advisory role (AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Novartis, Otsuka, Pierre Fabre), research funding (ARIAD). R.M. Huber: Honoraria (ARIAD, AstraZeneca, BMS, Boehringer Ingelheim, Pfizer, Roche), consulting or advisory role (BMS, Boehringer Ingelheim, Celgene, Clovis Oncology, Eli Lilly, Novartis, Roche), research funding (Pierre Fabre). L.A. Bazhenova: Stock and other ownership interests (Epic Sciences), honoraria (Novartis), consulting or advisory role (AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Genoptix, Heat Biologics, Pfizer, Roche/Genentech, Seattle Genetics, Trovagene), speakers bureau (AstraZeneca, Novartis, Pfizer, Roche/Genentech), research funding (AbbVie, ARIAD, Astellas, Astex, AstraZeneca/MedImmune, Boehringer Ingelheim, Chugai, Clovis Oncology, Eisai, Eli Lilly, Heat Biologics, Johnson & Johnson, Merck, Mirati, NanoCarrier, Novartis, Pfizer, Roche/Genentech). S-H.I. Ou: Advisory board (ARIAD). W. Reichmann, J. Haney, D. Kerstein: Employment, stock and other ownership interests (ARIAD). D.R. Camidge: Honoraria (ARIAD), research funding (ARIAD). S.N. Gettinger: Consulting or advisory role (ARIAD, BMS, Janssen), research funding (ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech). All other authors have declared no conflicts of interest.

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