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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

EudraCT: 2018-000399-13.

Editorial acknowledgement

Legal entity responsible for the study

University of Cologne.

Funding

Janssen-Cilag.

Disclosure

L. Nogova: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Novartis, Pfizer, Takeda, Roche; Financial Interests, Institutional, Other, IIT funding: Pfizer, MSD, Dracen, Bristol Myers Squibb; Financial Interests, Institutional, Other, IIT: Pfizer, MSD, Dracen, Bristol Myers Squibb, Amgen. A. Hillmer: Financial Interests, Institutional, Funding: Dracen. I. Terjung: Financial Interests, Institutional, Funding: Janssen, Novartis, Bristol Myers Squibb, Siemens. S. Merkelbach-Bruse: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Novartis, BMS, Janssen, GSK, Qiagen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, BMS, Janssen, GSK, Qiagen. J. Siemanowski: Financial Interests, Personal, Advisory Board: MDK; Financial Interests, Personal, Invited Speaker: Biocartis, Targos, Merck, molecular health and AstraZeneca. M. Scheffler: Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Takeda, Pfizer, Roche, Sanofi-Aventis; Financial Interests, Personal, Advisory Board: Amgen, Boehringer Ingelheim, Roche, Novartis, Amgen, Takeda, Pfizer, Pfizer, Amgen, Takeda, Janssen, Amgen; Financial Interests, Personal, Writing Engagement: Amgen; Financial Interests, Institutional, Local PI: Dracen Pharmaceuticals; Financial Interests, Institutional, Coordinating PI: Amgen, Dracen, Siemens Healthineers; Financial Interests, Personal, Steering Committee Member: Boehringer Ingelheim; Non-Financial Interests, Advisory Role, Patient advocacy: zielgenau e. V., YesWeCan(cer); Non-Financial Interests, Principal Investigator, YouTube channel for patients: OncoEducation. H. Hummel: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Boehringer Ingelheim; Financial Interests, Institutional, Coordinating PI: Amgen; Financial Interests, Institutional, Local PI: Amgen, Revolution Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Merck, Novartis, AstraZeneca, Dracen, Daiichi Sankyo, AvenCell Europe GmbH, Celgene; Financial Interests, Personal, Steering Committee Member: Amgen; Non-Financial Interests, Principal Investigator: AIO-Studien-gGmbH, Lung Cancer Group Cologne. M. Wermke: Financial Interests, Personal, Invited Speaker: Lilly, Boehringer Ingelheim, SYNLAB, Janssen, Merck Serono, Merck Serono, GWT, Amgen, Novartis; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Lilly, Boehringer Ingelheim, ISA Pharmaceuticals, Amgen, Immatics, Bayer, ImCheck Therapeutics; Financial Interests, Institutional, Funding: Roche; Financial Interests, Personal, Other: Pfizer, Bristol Myers Squibb, AstraZeneca, Amgen, GEMoaB, Sanofi/Aventis, Immatics, Merck Serono. C. Grohe: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, AstraZeneca, Lilly, Roche, Novartis, MSD Oncology, Takeda; Financial Interests, Personal, Advisory Board: MSD Oncology, AstraZeneca, Boehringer Ingelheim; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Other: Roche, Boehringer Ingelheim, Bristol Myers Squibb. N. Reinmuth: Financial Interests, Personal, Invited Speaker, including Ad-Boards: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Hoffmann-La Roche, Lilly, Pfizer, Takeda, Merck; Financial Interests, Personal, Invited Speaker, including Advisory Boards: Bristol Myers Squibb, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Invited Speaker: Sanofi. F. Griesinger: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Celgene, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda; Financial Interests, Institutional, Funding: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda. R. Thomas: Financial Interests, Personal and Institutional, Other: NEO New Oncology, PearlRiver Bio, Centessa, Disco Pharmaceuticals, Roche. R. Büttner: Financial Interests, Personal, Leadership Role: Argos Molecular Path Inc; Financial Interests, Personal and Institutional, Other: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Illumina, Janssen, Lilly, Merck-Serono, MSD, Novartis, Qiagen, Pfizer, Roche. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. All other authors have declared no conflicts of interest.