1329P FIND: A phase II study to evaluate the efficacy of erdafitinib in FGFR-altered NSCLC

Alterations in FGFR1-4 genes have oncogenic capability with sensitivity to kinase inhibition in several solid tumours and hematological malignancies. FGFR alterations occur in approximately 2% of non-small cell lung cancer (NSCLC) patients (pts), predominantly with squamous cell histology (sqNSCLC). We present results of a study evaluating the efficacy of the selective FGFR1-4 inhibitor erdafitinib in pts with FGFR-altered NSCLC. NSCLC pts were screened within the national Network of Genomic Medicine for FGFR mutations/translocations. Molecular eligibility was based on available preclinical and clinical data to FGFR alterations and assessed by a study specific molecular board. Pts were treated with erdafitinib in 3 cohorts: High confidence activating FGFR translocations (1), high confidence activating FGFR mutations (2) and low confidence activating FGFR alterations (3). The primary objective was the best confirmed overall response (OR) on erdafitinib in the cohorts 1 and 2 assessed by RECIST 1.1 every 8 weeks. Pts were treated until disease progression or unacceptable toxicity. Tumor samples and blood were collected before treatment and at disease progression. Sample size calculation was based on Simon’s two-stage minimax design. Evidence of efficacy was defined as 1/8 OR in the first and 4/15 ORs in the second stage for cohort 1 and 2 separately. Between 7/2019 and 9/2022, 26 pts were enrolled, 4 pts failed screening. The majority of pts were male (77%) and had sqNSCLC (73%). All pts were current or previous smokers. Of 22 pts on erdafitinib, 7 were in the cohort 1, 8 in the cohort 2 and 7 pts in the cohort 3. FGFR3-TACC3 fusions were the most frequent genetic alterations. In the cohort 1, two pts achieved partial response (PR). However, one PR remained unconfirmed (uPR). The best response in the cohort 2 was stable disease. The most observed adverse events of any grade were hyperphosphatemia in 50% and diarrhea in 45% of pts. According to the first stage results of the two-stage Simon’s design, erdafitinib showed preliminary efficacy in NSCLC with FGFR translocations. Further molecular, pharmacological and clinical data are needed to evaluate the efficacy of FGFR inhibition in NSCLC, especially in pts with FGFR mutations.