Pemigatinib Safe, Demonstrates Encouraging Responses Among Patients With Advanced Malignancies and an FGFR Mutation: FIGHT-101 Trial

Vivek Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, overviews the FIGHT-101 trial on pemigatinib, a selective FGFR 1-3 inhibitor, which targets mutations across a variety of tumor types.

Transcript
I'm Dr. Vivek Subbiah from the University of Texas, MD Anderson Cancer Center. It's a pleasure and honor to talk to you all about the FIGHT-101 study. As we know, the circulating fibroblast growth factor (FGFR) signaling, resulting from somatic FGFR alterations, that include activating mutations, amplifications and fusions rearrangement has been implicated in numerous tumor types, that include bladder cancer, breast cancer, cholangiocarcinoma, lung cancer, among multiple bowel cancers as well.

FGFR alterations occur across a wide variety of tumor types, including FGFR2 fusions, FGFR3 mutations. FGFR3 mutations and fusions are seen in bladder cancer. And FGFR2 fusions and rearrangements are predominantly seen in cholangiocarcinoma, among other cancers. There is increasing evidence for FGFR alterations, as drivers of tumorigenesis. And this has prompted the development of multiple FGFR targeted inhibitors in various solid tumors, including urothelial cancer and cholagiocarcinoma.

This was a first-in-human phase one study of this drug pemigatinib. This study was called FIGHT-101. Patients received pemigatinib monotherapy. Safety, tolerability, the pharmacokinetic and pharmacodynamic profile of pemigatinib was investigated as well. We also sought to look into the relationship between the efficacy outcomes of different FGF and FGFR alterations in multiple tumor types.

We enrolled 128 patients on this pemigatinib FIGHT-101 study. Patients, depending upon where they were enrolled on the study, received the dosing anywhere from one to 20 milligrams once daily intermittently in different dosing schedules, two weeks on, one week off or continuously. The two week on, one week off schedule was in 70 patients and 58 patients received continuous dosing. Interestingly, there were no dose limiting toxicities reported. We found out that the doses more than equal to 4 milligrams were pharmacologically active. In fact, the maximum tolerated dose, as we would define in the chemo error was not reached, but the recommended phase 2 dose given upon the PK and PD data was determined to be 13.5 milligram orally once daily.

The most common treatment emergent adverse event (TEAE) was on target toxicity of hyperphosphatemia. In fact, we saw hyperphosphatemia in 75% of patients and over grade three was in 2.3%. The most common grade three TEAE beyond hyperphosphatemia was fatigue. Again, dose reduction, dose interruption, and treatment emergent adverse event related discontinuation occurred in 66 patients and 13 patients.

Overall, interestingly, even in this first in human phase one study with patients being treated in multiple dose levels, we saw 12 partial responses, most commonly in cholangiocarcinoma. But beyond cholangiocarcinoma, we saw responses in a broad spectrum of tumor types, including head and neck cancer, treatment refractory pancreatic cancer, gallbladder cancer, uterine cancer, bladder cancer, brain tumors like recurrent pilocytic astrocytoma, and non-small lung cancer.

The median duration of response was 7.3 months. The overall response rate was highest in the patients that harbored the FGFR fusions or FGFR rearrangements. And it was 25% followed by those patients that harbored FGFR mutations and the response rate in the FGFR mutation cohort was 23%. Thank you.