Abstract 63P
Background
Aberrant signaling through the fibroblast growth factor receptor (FGFR) due to activating somatic alterations (mutations, amplifications, and fusions or rearrangements) has been associated with multiple malignancies. FGFR inhibitors (FGFRi) with distinct profiles are in clinical development.
Methods
Demographic and clinical data were collected for patients enrolled in FGFR-targeting trials conducted at the SCRI UK between Jan/12-Aug/23.
Results
55 patients across 7 phase 1/2 trials were identified. 45 (81.8%) were known to harbour a somatic FGFR alteration, mainly FGFR2 rearrangements (n=16; 35.6%), FGFR1/2 amplifications (n=13 each; 28.9%). 21.8% of patients harbored >1 FGFR alteration. Most frequent primary tumours were cholangiocarcinomas (n=17; 30.9%), urothelial (n=9; 16.3%) and colorectal cancers (n=8; 14.5%). Median lines of prior therapy was 3 (range 1-12); 83.6 % were FGFRi-naïve, 49% were male, median age at enrolment was 55 (range 35-80); ECOG PS 0-1 (100%). Three patients (5.4%) received an FGFRi in combination with a PD-1 inhibitor. All patients experienced at least an adverse event (AE), regardless of relatedness. The most commonly observed AEs were hyperphosphatemia (n=22, 40%), dry mouth (n=19; 34.5%), fatigue (n=14; 25.4%), mucositis (n=12; 21.8%;), nail changes (n=12; 21.8%), nausea (n=10; 18.2%,), and PPE (n=10; 18.2%). Treatment related Grade 3 AEs were recorded for 14 patients; dose reduction rate was 25.4% and drug discontinuation was 3.6%. No G4-5 events were observed. Best response was partial response in 13 patients (23.6 %) and stable disease in 26 patients (47.2%), with most responses being driven by rearrangements (52.7%) and amplifications (45.5%). Median PFS was 3.3 months (0.2-32.9) and median OS was 7.2 months (0.2-72.8). Three patients are still receiving treatment, without evidence of progressive disease.
Conclusions
Pooled data from early phase trials examining FGFRi indicate that they may be effective for patients with advanced solid tumors harboring FGFR alterations, with on-target toxicities manageable in most patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Arkenau: Financial Interests, Institutional, Full or part-time Employment: Ellipses. V. Subbiah: Financial Interests, Personal, Advisory Board, One time advisory board: Incyte, Novartis, Eli Lilly/Loxo Oncology, Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Board, One time ad board: Roche, Pfizer; Financial Interests, Institutional, Advisory Board, Scientific Advisory Board: Relay Therapeutics; Financial Interests, Institutional, Advisory Board: Regeneron; Financial Interests, Institutional, Advisory Board, Consultancy one time service: Novartis; Financial Interests, Personal, Invited Speaker, Invited speaker: Clinical Care Communications; Other, Personal, Other, I am an employee of Sarah Cannon Research Institute, Nashville, TN: Sarah Cannon Research Institute. E. Fontana: Financial Interests, Personal, Invited Speaker: CARIS Life Science, Repair Therapeutics; Financial Interests, Personal, Other, Conference attendance: Sapience Pharma; Financial Interests, Personal, Full or part-time Employment: Hospital Corporation of America (HCA) International; Financial Interests, Personal, Officer: EORTC; Financial Interests, Institutional, Invited Speaker: Repair Therapeutics, Bicycle Therapeutics, Artios Pharma, Seagen, Amgen, Nurix Therapeutics, BioNTech SE, Relay Therapeutics, Taiho Pharmaceutical, Pfizer, Roche, Daiichi Sankyo, Gilead Science, Basilea Pharmaceutica, Jiangsu Hengrui Medicine, Mereo Biopharma, Hutchmed, Merus, Crescendo Biologics, GSK plc, BeiGene, Turning Point Therapeutics, Sapience Pharma; Non-Financial Interests, Personal, Advisory Role: Vivan Therapeutics. All other authors have declared no conflicts of interest.