NEW YORK – Basel, Switzerland-based Basilea Pharmaceutica on Monday announced that it has begun a Phase I/II trial evaluating its investigational agent derazantinib as a treatment for patients with advanced gastric cancer whose tumors have FGFR alterations.
The study, dubbed FIDES-03, will assess derazantinib, an inhibitor of FGFR1, FGFR2, and FGFR3, both as a monotherapy and in combination with the PD-L1 inhibitor atezolizumab (Roche's Tecentriq). Basilea will sponsor the study, while Roche will supply atezolizumab.
Basilea is also conducting two additional studies involving derazantinib, an agent that it licensed from ArQule (now a subsidiary of Merck) in 2018. One of these studies, a Phase II registrational trial dubbed FIDES-01, is assessing derazantinib as a treatment for patients with inoperable or advanced intrahepatic cholangiocarcinoma. That trial has two arms, one enrolling patients whose tumors harbor FGFR2 gene fusions as determined by fluorescence in situ hybridization (FISH), and the other involving patients whose tumors harbor FGFR2 amplifications or mutations as determined by next-generation sequencing.
The second clinical study, FIDES-02, is evaluating derazantinib both alone and in combination with atezolizumab as a treatment for patients with advanced urothelial carcinoma characterized by FGFR gene aberrations.
"Our development strategy for derazantinib is focused on strengthening the clinical evidence on the differentiation versus other FGFR inhibitors," Basilea Chief Medical Officer Marc Engelhardt said in a statement. "The unique kinase inhibition profile of derazantinib, results from preclinical studies, and the safety and tolerability profile observed in clinical studies provide a strong rationale for evaluating the drug candidate in patients with advanced gastric cancer with FGFR genetic aberrations, both as monotherapy and in combination therapy."
FGFR inhibitors are an active area for precision oncology drug development. The US Food and Drug Administration last year granted accelerated approval to Janssen Pharmaceutical's pan-FGFR inhibitor erdafitinib (Balversa) for metastatic bladder cancer patients who have progressed on platinum-based chemotherapy and who harbor alterations in FGFR3 or FGFR2 genes. A year later, the agency approved pemigatinib (Incyte's Pemazyre), an inhibitor of FGFR isoforms 1, 2, and 3, for previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements.
Recently, Relay Therapeutics began the first-in-human study of RLY-4008 in FGFR2-altered intrahepatic cholangiocarcinoma and other advanced solid tumors.