Gunagratinib Granted Orphan Drug Designation for Cholangiocarcinoma

Gunagratinib (ICP-192), a potential therapeutic option for patients with cholangiocarcinoma, has been granted an orphan drug designation by the FDA.

Gunagratinib (ICP-192), a potential therapeutic option for patients with cholangiocarcinoma, has been granted an orphan drug designation by the FDA.

Data from the first-in-human phase 1/2a ICP-CL-00301 trial (NCT03758664) presented during the 2021 ASCO Annual Meeting showed that among 12 patients with FGF/FGFR gene aberrations who completed at least 1 tumor assessment, gunagrabtinib induced an overall response rate (ORR) of 33.3% (n = 4).2

Of these responders, 1 patient with cholangiocarcinoma (8.3%) achieved a complete response, 3 (25%) experienced a partial response, and 7 had stable disease. Moreover, the disease control rate with the agent was 91.7% (n = 11).

“We are very proud that our solid tumor drug has been granted orphan drug designation by the FDA following that for our blood cancer drug,” Jasmine Cui, PhD, co-founder, chairwoman, and chief executive officer of InnoCare, stated in a press release. “Gunagratinib demonstrated antitumor activity for multiple tumor types, including cholangiocarcinoma, in patients with FGF/FGFR gene aberrations. We will rapidly advance the multicenter multi-indication clinical trials in both the United States and China in order to benefit patients early.”

The FGFR signaling pathway has been shown to represent a critical driver of tumorigenesis in several tumor types. The novel irreversible pan-FGFR inhibitor gunagratinib was developed to have strong antitumor activity with high target selectivity. The agent is hypothesized to be able to overcome acquired resistance to first-generation ATP-competitive FGFR inhibitors.

In the phase 1/2a dose-escalation and -expansion trial, investigators set out to examine the safety and efficacy of gunagratinib in patients with advanced solid tumors. The dose-escalation portion of the research enrolled patients with advanced solid tumors who had previously received standard treatment that had failed. Doses ranged from 2 mg once daily up to 16 mg once daily.

In the dose-expansion phase of the trial, the agent is being evaluated at a once-daily dose of 12 mg in 25 patients. For this portion of the research, patients needed to have previously received at least 1 systemic frontline chemotherapy regimen and they needed to have cholangiocarcinoma that harbored FGFR2 translocations or fusions.

Investigators noted a dose-dependent increase of plasma exposure and linear pharmacokinetic properties of the agent. Moreover, an increase in serum phosphorus with gunagratinib was observed when the drug was administered at a once-daily dose of 8 mg or higher.

Regarding safety, no dose-limiting toxicities were reported with the agent. Moreover, the maximum-tolerated dose of gunagratinib had not yet been reached. Notably, no central serious retinopathy/retinal pigment epithelial detachment was observed.

Among 30 patients included in the safety analysis, across the dose-escalation phase of the trial (n = 23) and the dose-expansion phase (n = 7), treatment-related toxicities reported in 20% or more of patients included metabolism and nutrition disorders like hyperphosphatemia (73.33%), hypercalcemia (33.33%), and hypertriglyceridemia (26.67%); increased aspartate aminotransferase (26.67%) or alanine aminotransferase (23.33%), and increased blood uric acid (20.00%). Moreover, diarrhea was reported in 26.67% of patients.


  1. InnoCare announces orphan drug designation of gunagratinib by US FDA for treatment of cholangiocarcinoma. News release. InnoCare Pharma. June 16, 2021. Accessed June 17, 2021.
  2. Guo Y, Yuan C, Ying J, et al. Phase I result of ICP-192 (gunagratinib), a highly selective irreversible FGFR inhibitor, in patients with advanced solid tumors harboring FGFR pathway alterations. J Clin Oncol. 2021;39(suppl 15):4092. doi:10.1200/JCO.2021.39.15_suppl.4092

This article was originally published on OncLive as "FDA Grants Orphan Drug Designation to Gunagratinib for Cholangiocarcinoma"