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 

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 

-positive, unresectable or metastatic cholangiocarcinoma.

Data presented at the 2022 ESMO Congress focused on patients with 

 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 

. 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.

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


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

Alison Schram, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the results of the phase 1/2 eNRGy trial (NCT02912949), which were presented during the 2021 ASCO Annual Meeting, in 

Findings from the eNRGy trial demonstrated a 29% overall response rate (ORR) with zenocutuzumab, an investigational bispecific antibody, in patients with locally advanced, unresectable or metastatic, 

Confirmed partial responses (PRs) were observed in 42% of the 12 patients with 

 fusion–positive pancreatic ductal adenocarcinoma treated with the novel agent. An additional 50% of these patients derived stable disease from zenocutuzumab, Schram says. In this cohort, 100% of patients with elevated CA 19-9 measurements experienced a decline of more than 50%, Schram explains. 

The ORR was 25% in the non–small cell lung cancer cohort (n = 24) and responses were observed irrespective of prior afatinib (Gilotrif) treatment, Schram says. In the basket cohort, one patient each with breast cancer and cholangiocarcinoma derived a PR, yielding a confirmed ORR of 22% in this cohort (n = 9), Schram says.

Notably, 40% of patients had treatment ongoing at the time of the data cut-off, Schram says. As such, zenocutuzumab could offer patients with heavily pretreated 

 fusion–positive solid tumors an effective treatment option, concludes Schram. 

Alison Schram, MD, discusses the results of the phase 1/2 eNRGy trial, which were presented during the 2021 ASCO Annual Meeting, in NRG1 fusion–positive solid tumors.  



Alison Schram, MD

Articles

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

Dr. Schram on the Results of the Phase 1/2 eNRGy Trial in NRG1+ Solid Tumors