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Virote Sriuranpong



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    OA02 - Novel Therapies in ROS1, HER2 and EGFR (ID 893)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 105
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      OA02.05 - CK-101 (RX518), a Third Generation Mutant-Selective Inhibitor of EGFR in NSCLC: Results of an Ongoing Phase I/II Trial (ID 11982)

      11:15 - 11:25  |  Author(s): Virote Sriuranpong

      • Abstract
      • Presentation
      • Slides

      Background

      CK-101 (also known as RX518) is a novel, oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and resistance mutations, with minimal activity on wild-type EGFR. CK-101 is being studied in an ongoing first-in-human, multicenter, Phase I/II trial in advanced non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations and other advanced malignancies in the US, Australia, New Zealand and Thailand (NCT02926768). Following dose escalation in which 18 pts received CK-101 in dose groups ranging from 100 mg to 1200 mg/day, a first dose-expansion cohort was enrolled at 400 mg bid.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Eligible pts in dose escalation had a confirmed diagnosis of NSCLC or any advanced solid tumor where targeting EGFR was reasonable. Eligible pts in dose-expansion had a confirmed diagnosis of either (1) EGFR mutation-positive advanced or metastatic NSCLC without prior exposure to EGFR-TKI therapy, or (2) T790M-positive advanced or metastatic NSCLC with disease progression on previous EGFR-TKI therapy, with no limit on number of prior lines of systemic therapy.

      4c3880bb027f159e801041b1021e88e8 Result

      As of 25 June 2018, 37 pts were treated in dose escalation and expansion and evaluable for safety; median age 59 years, 51% male, 51% Asian, 84% ECOG PS 1. No DLTs or treatment-related SAEs were reported. Most common treatment-emergent adverse events: nausea (16%), diarrhea (14%), lacrimation increased (14%) and vomiting (11%), all grade 1/2 except one grade 3 diarrhea; no grade 4. In dose-expansion, 19 pts were treated with CK-101 at a dose of 400 mg bid and evaluable for response; 8/19 (42%) pts were treatment-naïve, 6/19 (32%) pts had brain metastases; 16/19 (84%) pts remained on treatment. Disease control rate was 100% (19/19), with 16/19 pts (84%) experiencing target lesion reduction versus baseline and 8 pts achieving a partial response (7 confirmed, 1 pending confirmation). In treatment-naïve pts, 6/8 (75%) pts achieved a partial response. In pts with brain metastases, 3/6 (50%) pts achieved a partial response. Higher drug exposures were associated with higher response rate with a confirmed ORR of 55% (6/11) in pts achieving Cmax >400 ng/mL. Median duration of response and progression-free survival were not reached as of the data cutoff.

      8eea62084ca7e541d918e823422bd82e Conclusion

      CK-101 was well tolerated with a manageable safety profile. Durable anti-tumor activity was observed, particularly in treatment-naïve pts. Further study is ongoing to establish the optimal dose to maximize therapeutic effect in a planned Phase 3 study in treatment-naïve EGFR-mutant NSCLC pts.

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-104 - Plasma T-Cell-Derived Circulating DNA in Advanced NSCLC is Not Correlated with TIL but has a Potential of Prognostic Value (ID 13771)

      16:45 - 18:00  |  Author(s): Virote Sriuranpong

      • Abstract

      Background

      Non-tumor derived circulating DNA (nt-cirDNA) of advanced non-small cell lung cancer (NSCLC) patient, even not yet clear originated, was associated with prognosis. In this study, we investigated whether T-cell-derived circulating DNA (T-cirDNA) was the majority part of nt-cirDNA nor correlated with tumor-infiltrating T-lymphocyte (T-TIL).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Prognostic impact including demographic characteristics were integrated into the model. Using Quantitative real-time PCR with Taqman assay specific to VDJ segment of TCRβ (T-cell-receptor beta chain) was used to represented amount of T-cirDNA in plasma of 106 advanced stage NSCLC. Quantitative CD3-specific immunohistochemistry (IHC) staining from biopsy specimen, represented T-TIL, was done using Aperio ImageScope.

      4c3880bb027f159e801041b1021e88e8 Result

      T-cirDNA was detected in seventy-three advanced NSCLC patients with a median of 1.71 pg/ml [range 0-2260]. Forty-six patients were assessed for proportion of T-TIL per total cell with a median of 0.22 per mm2 [range 0.02-2.34]. No correlation was found between T-cirDNA and T-TIL. From multivariable analysis, active smoking status was the only factor correlated with low T-cirDNA level (P<0.001). Kaplan Meier survival analysis of T-cirDNA ratio (T-cirDNA/total cirDNA) shown a trend of favor prognostic outcome for high T-cirDNA ratio (more than 0.03 %), HR 0.67 [95% CI 0.43-1.04, P=0.07]media2.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      plasma T-cirDNA component, even not correlated with T-TIL, revealed a trend of prognostic impact in advanced stage non-small-cell cancer patients.

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