In a preplanned interim analysis of a phase 2 trial, derazantinib (ARG 087) demonstrated antitumor efficacy and met the prespecified threshold for the trial to proceed to the next stage as planned for patients with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions, mutations, or amplifications, according to a press release from Basilea Pharmaceutica Ltd.
“We are very pleased with the positive interim results for this cohort of iCCA patients with FGFR2 gene mutations or amplifications. The clinical benefit with derazantinib is similar to that reported for iCCA patients with FGFR2 gene 2/4 fusions earlier this year,” Marc Engelhardt, MD, chief medical officer of Basilea, said in a statement. “This supports the relevance of derazantinib in a group of patients with iCCA where there has been very limited clinical evidence of successful treatment with other FGFR inhibitors and confirms the broad potential of derazantinib as a monotherapy for the treatment of iCCA patients with diverse FGFR2 genetic aberrations.”
The FIDES-01 (Fibroblast growth factor Inhibition with DErazantinib in Solid tumors) study (NCT03230318) looked at patients in 2 cohorts receiving oral derazantinib at 300 mg once a day. Cohort 1 investigated those with iCCA and FGFR2 gene fusions for clinical proof of concept, and cohort 2 investigated those with iCCA and FGFR2 gene mutations or amplifications.
In cohort 2, there were 14 evaluable patients who received at least 1 post-baseline tumor assessment. Since over 8 patients met the primary end point of obtaining progression-free survival (PFS) of at least 3 months in the second cohort, the prespecified criterion was achieved. The trial will now be able to enroll 43 patients and advance to the next stage.
At the time of the interim analysis, the median PFS had not been reached since multiple patients were still on treatment. The median PFS will be defined at a later time point. However, the proportion of patients with complete response (CR), partial response (PR), or stable disease (SD) was 79%. This disease control rate included 1 patient with confirmed CR, 1 patient with unconfirmed PR, and 9 patients with SD as their best response at the time of the interim analysis.
Investigators observed a consistent safety and tolerability profile with derazantinib in cohort 1.
In the first cohort, the primary end point was the objective response rate. Secondary end points for the trial were safety, duration of response, PFS, overall survival, and health-related quality of life.
Patients enrolled on the FIDES-01 study had to have radiographic progression of bile duct cancer on at least 1 prior systemic therapy, measurable disease by RECIST v1.1 criterion, ECOG performance status of 0 or 1, and adequate organ function. If patients had received major or locoregional surgery, or radiation therapy within 4 weeks of the first dose of derazantinib, previous FGFR inhibitors, or one chemotherapy or antibody cycle interval, they were excluded from the trial.
Derazantinib, an investigational small-molecule FGFR inhibitor, has strong activity against FGFR1, 2, and 3. Key drivers of cell proliferation, differentiation, and migration are FGFR kinases. FGFR genetic aberrations are found in multiple cancer types, including iCCA, lung, breast, gastric, and urothelial cancer, at a range of 5% to 30%.
“This outcome is very encouraging and further strengthens the evidence for the differentiation of derazantinib versus other FGFR inhibitors both from the efficacy and safety perspective. We are now progressing the study to the next stage and expect topline results for cohort 2 in the first half of 2022,” Engelhardt concluded.
Basilea reports positive interim results from phase 2 study FIDES-01 for derazantinib in FGFR2 gene mutation- or amplification-positive patients with bile duct cancer (iCCA). News release. Basilea. Published March 24, 2021. Accessed March 25, 2021. https://bit.ly/2O1gNWE