Author of

• 36267

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  P75 - Immunotherapy (Phase II/III Trials) - Misc. Topics (ID 248)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Immunotherapy (Phase II/III Trials)
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 36268

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    P75.01 - Activity of Brigatinib in Alectinib-Resistant ALK-Positive NSCLC According to ALK Plasma Mutation Status From J-ALTA Trial (ID 3615)

    00:00 - 00:00  |  Presenting Author(s): Toyoaki Hida
    • Abstract
    • Slides

    Introduction
    

    Brigatinib is a selective and potent ALK tyrosine kinase inhibitor (TKI) with preclinical activity against wild-type ALK and a broad spectrum of ALK secondary mutants, known to confer clinical resistance to crizotinib, ceritinib, and alectinib. Brigatinib has shown promising efficacy in Japanese patients with ALK+ NSCLC previously treated with alectinib in a phase 2 trial (J-ALTA). As an exploratory correlative analysis, we examined the relationship of ALK mutation status with brigatinib treatment outcome by NGS analysis of cell free DNA (cfDNA) using plasma specimens at baseline prior to brigatinib treatment (baseline [BL]) in ALK+ NSCLC patients who progressed on alectinib or other ALK TKIs and enrolled in this study.

    Methods
    

    Plasma samples were analyzed using the PGDx elio^TM plasma resolve (Personal Genome Diagnostics, Baltimore, MD, USA) to determine ALK kinase domain mutations and EML4-ALK fusion status. Brigatinib activity was defined by the confirmed objective response rate (ORR) (RECIST v1.1). Data are reported as of January 22, 2019 for J-ALTA trial.

    Results
    

    Of the 72 ALK+ NSCLC patients enrolled, evaluable plasma samples were obtained from 70 patients at BL; alectinib was the most recent ALK TKI (with or without prior crizotinib) in 51 patients. Of these, 30.0% (21/70) of patients had confirmed response to brigatinib, and 35.3% (18/51) of post-alectinib patients responded to brigatinib. Secondary ALK mutations were detected in plasma in 15.7% (11/70) of patients (10 post-alectinib and 1 post-ceritinib). ORR was confirmed in 45.5% (5/11) of these patients. Best responses in patients with secondary ALK mutations were: 5 confirmed partial responses (PRs); 4 stable disease (SD); 2 progressive disease (PD), including 1 confirmed PR and 2 SD in patients with ALK G1202R mutation at BL. No secondary ALK mutations were detected in 84.2% (59/70), ORR was confirmed in 27.1% (16/59) of these. Gene amplification was detected in only 1 patient (MYC gene amplification).
    
    BL EML4-ALK fusion was detected in 51.4% (36/70) of the post-ALK TKIs patients; 25.0% (9/36) of these had secondary ALK mutations. Post-BL samples were also collected from 49 patients at the end of brigatinib treatment. Secondary ALK mutations were detected in 7 patients: 1 with F1174L (also had G1202R at BL); 1 with E1210K (also had I1171S at BL); 5 with G1202R (2 not present at BL; 2 present at BL; 1 present at BL and S1206F also detected). MYC gene amplification was detected in 2 patients.

    Conclusion
    

    ALK fusions were detected in the plasma of over 50% of ALK+ NSCLC patients resistant to alectinib and/or other TKIs. Brigatinib demonstrated meaningful activity in ALK TKI-resistant patients regardless of the presence of secondary ALK mutations and EML4-ALK fusion status in plasma. Clinical trial information: NCT03410108.

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