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Leora Horn



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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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      182TiP - A phase II trial of tepotinib in patients with non-small cell lung cancer (NSCLC) harboring MET alterations: The VISION study (ID 452)

      12:30 - 13:00  |  Author(s): Leora Horn

      • Abstract
      • Slides

      Background

      Dysregulation of the MET pathway is common in human carcinomas and leads to dependency on MET signalling, representing a potential therapeutic target in NSCLC. MET alterations including MET-exon 14 skipping mutations (METex14) and MET amplification (METamp) are known oncogenic drivers, and occur in 3–4% and 0.4–1.5% of NSCLCs, respectively. Tepotinib, a potent selective, small molecule MET inhibitor, has shown promise in preclinical and phase 1 trials.

      a9ded1e5ce5d75814730bb4caaf49419 Trial design

      VISION (NCT02864992), a single-arm, open-label, multicentre Phase 2 trial, will assess the antitumour activity and tolerability of tepotinib 500 mg daily, as 1st–3rd line of treatment, in patients with histologically-confirmed, advanced (stage IIIB/IV) NSCLC (all histologies) harboring MET alterations. Patients with METex14 + (determined by tumor biopsy [TBx] and/or plasma ‘liquid’ biopsy [LBx]; Cohort A) or METamp (determined by LBx; Cohort B) NSCLC are included. Prior treatment with checkpoint inhibitors is permitted. Patients with epidermal growth factor receptor-activating mutations, anaplastic lymphoma kinase rearrangements, or with brain metastasis as the only measurable lesion are excluded. The primary endpoint is objective response rate (ORR) by independent review committee via Response Evaluation Criteria in Solid Tumors v1.1. Secondary objectives include investigator-assessed ORR, duration of response, disease control, progression free survival, overall survival, tolerability, and safety. Adverse events (AEs) will be monitored throughout the study and for 30 days (90 days for serious AEs) after treatment and graded per National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. Enrolment into Cohort A commenced in September 2016 and is continuing. Enrolment of patients with LBx-confirmed METamp into Cohort B commenced in September 2018; based on an interim analysis of 12 patients, recruitment may continue to enrol ≥60 patients. This abstract was previously presented at ESMO Asia 2018, FPN 546TiP, Paik et al. Reused with permission.

      d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification

      NCT02864992.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Lisa Jolly, Bioscript Science (Macclesfield, UK).

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      Merck KGaA.

      213f68309caaa4ccc14d5f99789640ad Funding

      Merck KGaA.

      682889d0a1d3b50267a69346a750433d Disclosure

      P. Paik: Advisory board, honorarium: Celgene; IDMC: Takeda. A. Cortot: Advisory boards member: AstraZeneca, BMS, MSD, Pfizer, Novartis, Roche, Takeda, Boehringer Ingelheim; Corporate-sponsored research: Merck. E. Felip: Speaker’s bureau, advisory board: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celegene, Eli Lilly, Guardant Health, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, AbbVie, Merck. J. Mazieres: Advisory board: Roche, BMS, MSD, AstraZeneca, Pfizer, Novartis. F. Griesinger: Scientific support: ASTRA, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens; Talks, presentations, advisory boards: ASTRA, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, ARIAD, AbbVie, Siemens. R. Bruns, J. Scheele, J. Straub: Employee: Merck KGaA, Darmstadt, Germany. R. Veillon: Congress registration, advisory board: Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Pfizer, AbbVie, Merck. All other authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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    Mini Oral session I (ID 60)

    • Event: ELCC 2019
    • Type: Mini Oral session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 08:00 - 08:50, Room A
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      112O - Circulating tumor (ct) DNA analysis to monitor response and resistance to ensartinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) (ID 555)

      08:00 - 08:50  |  Presenting Author(s): Leora Horn

      • Abstract
      • Presentation
      • Slides

      Background

      Pts with anaplastic lymphoma kinase (ALK)-rearranged NSCLC have benefited from ALK tyrosine kinase inhibitors (TKIs); however, most pts eventually acquire resistance. Identification of resistance mutations informs subsequent therapy but has typically required invasive repeat biopsies. Here, we assessed the utility of ctDNA analysis and the ability to monitor response longitudinally and detect resistance mutations during therapy with ensartinib, a potent second-generation ALK TKI.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      Blood samples were collected from pts at the start of and during treatment with ensartinib in the eXalt2 trial (NCT01625234). DNA from plasma samples was hybridized to a panel of probes using the Resolution Biosciences targeted hybrid-capture system. Archival tumor tissue from a subset of pts was analyzed for comparison. Efficacy assessments included response rate (RR) and median progression-free survival (mPFS).

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      As of April 1, 2018, baseline plasma samples from 76 pts with ALK+ NSCLC were analyzed. Among these pts, 22% were ALK-TKI naive, 49% received prior crizotinib, and 29% received crizotinib and ≥ 1 second-generation ALK TKI. There was a high concordance rate (91%) between plasma and tissue analysis of ALK fusions. Among 69 efficacy-evaluable pts, the EML4-ALK variant 1 (V1) and V3 were detected at baseline in 17 pts (24%) and 7 pts (10%), respectively, and 12 pts (17%) had non-V1 or non-V3 fusions. Both RR and mPFS with ensartinib were more favorable in pts with V1 vs V3 fusions (9/17 [53%] vs 1/7 [14%] and 8.2 vs 1.9 months, respectively). The pooled RR of pts with other EML4-ALK variants was 7/12 (58%). Longitudinal plasma samples were analyzed in 11 pts. In general, reduced allelic frequencies (AFs) of ALK fusions were detected during clinical response, followed by increased AFs and/or the emergence of new mutations in ALK at or before disease progression.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Overall, the data suggest that plasma ctDNA analysis can potentially identify a subgroup of pts with ALK+ NSCLC who may derive clinical benefit from ensartinib. Furthermore, serial assessments of ctDNA during therapy offer a convenient method to track tumor response and identify the mutational landscape of acquired resistance.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT01625234.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Writing and editorial support was provided by Chrysalis Medical Communications funded by Xcovery Holding Company, LLC.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      Xcovery Holding Company, LLC.

      213f68309caaa4ccc14d5f99789640ad Funding

      Xcovery Holding Company, LLC.

      682889d0a1d3b50267a69346a750433d Disclosure

      L. Horn: Consultant/Advisory board member: AbbVie, AstraZeneca, Bristol-Myers Squibb, Merck, Roche-Genentech, Xcovery; Commercial research support: Boehringer Ingelheim. H. Wakelee: Commercial research grants: Genentech/Roche, Novartis, Pfizer, Xcovery; Consultant/advisory board member: AstraZeneca, Genentech/Roche (uncompensated), Merck (uncompensated), Novartis (uncompensated), ARIAD (uncompensated); Commercial research grants to institution for conduct of clinical trial work: Genentech/Roche, Novartis, Pfizer, Lilly, Celgene, Astrazeneca/Medimmune, Exelixis, Clovis Oncology, BMS, Gilead, Pharmacyclics, ACEA biosciences, Merck, Xcovery. K.L. Reckamp: Consultant/advisory board member: ARIAD; Commercial research grants: Xcovery; Consultant/advisory board member: ARIAD Takeda, Exelixis, Guardant, Loxo, Genentech; Commercial research grants: Xcovery, AbbVie, Acea, Adaptimmune, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Guardant, Janssen, Loxo Oncology, Seattle Genetics, Takeda, Zeno. C.M. Lovly: Consultant: Pfizer, Novartis, AstraZeneca, Genoptix, Sequenom, ARIAD, Takeda, Foundation Medicine, Blueprints Medicine, Cepheid; Research funding: Novartis, AstraZeneca, Xcovery (through Vanderbilt University); Work in the CML laboratory is supported through the National Institutes of Health (NIH) and National Cancer Institute (NCI) R01CA121210 and P01CA129243, the Damon Runyon Foundation, the LUNGevity Foundation, the V Foundation, the Lung Cancer Foundation of America, and the International Association for the Study of Lung Cancer. CML was also supported through P30CA6848. J. Hernandez, T. Shaffer, K. Garg, L.P. Lim, M. Li: Employee, shareholder: Resolution Bioscience. S. Patel: Sci Ad Board member: AZ, BMS, Illumina, Tempus, Novartis; Research funding: BMS, Eli Lilly, Fate, Incyte, AZ/MedImmune, Merck, Pfizer, Roche/Genentech, Xcovery, Fate Therapeutics, Genocea, and Iovance; Research funds through UCSD. R.E. Sanborn: Consultant/advisory board member: ARIAD, Takeda. A. Holzhausen: Employee: Xcovery Holdings, Inc. K. Harrow, C. Liang: Employee, ownership interests (including patents): Xcovery Holding, Inc. All other authors have declared no conflicts of interest.

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