Publication

Video

Supplements and Featured Publications
Novel Therapeutic Approaches to Target FGFR2 Mutations in Cholangiocarcinoma
Volume 1
Issue 1

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

Alison Schram, MD, discusses the efficacy and safety of RLY-4008 in patients with cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.

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.

Related Videos
Edward B. Garon, MD, MS
Heinz-Josef Lenz, MD, FACP
Emrullah Yilmaz, MD, PhD
Marc-Oliver Grimm, MD
Eric Winer, MD
Catherine E. Lai, MD, MPH
David Braun, MD, PhD
Fernando C. Maluf, MD, PhD
Monzr M. Al Malki, MD
Antonio Martin Jimenez Jimenez, MD