Dr. Schram on the Efficacy of RLY-4008 in FGFR2+ Cholangiocarcinoma

Alison Schram, MD, medical oncologist, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses the efficacy and safety of RLY-4008 in patients with cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.

In the phase 1/2 ReFocus trial (NCT04526106), investigators are examining the safety and preliminary efficacy of the next-generation FGFR2 inhibitor, RLY-4008, in patients with FGFR2-positive, unresectable or metastatic cholangiocarcinoma.

Data presented at the 2022 ESMO Congress focused on patients with FGFR2 fusion–positive, FGFR inhibitor–naïve cholangiocarcinoma, Schram says. Among patients treated across all dose levels (n = 38), the confirmed objective response rate (ORR) with RLY-4008 was 57.9% by RECIST v1.1 criteria. When administered at the recommended phase 2 dose (RP2D) of 70 mg daily (n = 17), the agent produced a confirmed ORR of 82.4%, Schram explains. In the all-dose population, 92% of patients experienced tumor reduction.

The safety profile with RLY-4008 was consistent with the preclinical data previously reported with the FGFR2 inhibitor, Schram adds. Notably, RLY-4008 spares FGFR1/FGFR3/FGFR4 while inhibiting FGFR2. As a result, hyperphosphatemia and diarrhea were uncommon, according to Schram. FGFR2-mediated toxicities reported with the agent included stomatitis, nail toxicity, and hand-foot syndrome, although most of these effects were low grade, Schram says. Additionally, 27% of patients who were given RLY-4008 at the RP2D required dose reductions, Schram concludes.