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Behzad Kharabi Masouleh

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-72 - FIND Trial: A Phase II Study to Evaluate the Efficacy of the FGFR-Inhibitor Erdafitinib in FGFR-Mutated and -Translocated Squamous NSCLC (ID 14185)

      16:45 - 18:00  |  Author(s): Behzad Kharabi Masouleh

      • Abstract


      Genomic FGFR alterations and their oncogenic driver potential are frequently observed in various cancers, including NSCLC, bladder cancer, glioblastoma, sarcoma and head and neck cancer. Initial clinical trials with selective FGFR inhibitors showed moderate responses in FGFR amplified squamous NSCLC (sqNSCLC) patients. However, in FGFR mutated or translocated tumor types (bladder cancer, glioblastoma, endometrial cancer) a response rate of above 30% was observed. Preclinical cell line and patient-derived sqNSCLC xenograft models with FGFR mutations or translocations indicate strong oncogenic activity and potential sensitivity to FGFR inhibitors. Thus, FGFR directed treatment in FGFR mutated and translocated sqNSCLC is of special interest. In particular as there is no approved targeted treatment in the squamous population representing about 25% of all NSCLC patients. Study challenges: Multiple FGFR translocations and mutations are known and approximately 3% of all sqNSCLC patients harbor somatic alterations within FGFR genes. However, only some of these mutations are shown to be oncogenic drivers in vitro and in vivo experiments or first in man trials. This is important given the many FGFR alterations with unknown biological significance and which confer potential resistance to FGFR inhibitors.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Screening for FGFR mutations/translocations will be performed within the national Network of Genomic Medicine (nNGM) in 15 screening centers in Germany. SqNSCLC patients with activating FGFR genetic alterations will be treated in 11 clinical centers in Germany with the selective FGFR1-4 kinase inhibitor erdafitinib. Archival samples, fresh frozen tumor samples and blood for circulating tumor DNA (ctDNA) will be collected before treatment. Patients will be treated until disease progression or unacceptable toxicity. At progression, fresh frozen tumor biopsies and ctDNA analyses will be performed to characterize resistance mechanisms.

      The primary objective of the trial is to analyze the efficacy of erdafitinib in sqNSCLC patients with FGFR genetic driver alterations. NSCLC patient number will be based on a statistical hypothesis aiming at increasing the response rate compared to chemotherapy / immunotherapy after standard treatment. The estimated number of patients is based on a 2-stage Simon design. Patients will be recruited into 3 cohorts: Cohort 1: high confidence activating FGFR translocations (max. 15 patients); Cohort 2: high confidence activating FGFR mutations (max. 15 patients); Cohort 3: low confidence activating FGFR alteration (ca. 20 patients)

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      The study is under development and is currently targeted to start recruitment in Q2/2018.