FDA Grants Orphan Drug Designation to Gunagratinib for Cholangiocarcinoma

The FDA has granted an orphan drug designation to gunagratinib (ICP-192) for the treatment of cholangiocarcinoma.

The FDA has granted an orphan drug designation to gunagratinib (ICP-192) for the treatment of cholangiocarcinoma, according to a press release by InnoCare.1

Gunagratinib, which is a selective pan-FGFR inhibitor, targets multiple solid tumors with FGFR gene aberrations. This is achieved through inhibiting FGFR activities by covalent binding. Preclinical data has found the agent is able to push past acquired resistance to first-generation reversible FGFR inhibitors such as infigratinib (Truseltiq).

The orphan drug designation is based on results of a phase 1/2 study presented at the American Society of Clinical Oncology’s Annual Meeting 2021. The single-group, open-label study has an estimated enrollment of 56 patients and an estimated completion date of December 2024. The primary outcome of the phase 1 dose escalation portion was adverse events (AEs). The primary outcome of the phase 2 dose expansion portion was objective response rate (ORR). Secondary outcomes include Cmax, AUC, apparent half-life for designation elimination phases, food effect, disease control rate (DCR), duration of objective response (DoR), progression-free survival (PFS), and correlation between FGFR aberrations with efficacy.

The study was comprised of a single-arm and followed a 3+3 dose escalation scheme. The starting dose level was 2 mg. Patients received the agent once daily in 21-days cycles until unacceptable toxicity or progression.2

In order to participate, patients must be between 18 and 75 years of age, have an unresectable or metastatic advanced malignant solid tumor, have a detectable FGFR2 translocation/fusion, has at least one evaluable lesion, and EGOC score of 0 or 1, and adequate organ function. Patients who have been previously treated with FGFR small molecule inhibitors or antibody drugs, have had major surgery within 6 weeks of the first dose, have significant gastrointestinal disorders that may interfere with absorption, metabolism, or excretion of the agent, central nervous system metastasis, clinically significant cardiovascular disease, or a history of organ transplantation or allogeneic hematopoietic stem cell transplantation are not eligible to participate.

As of February 2021, 30 participants have been treated with the agent. The median age of the patients was 55 years and 56.7% were male. The maximum tolerated dose has not been reached. For patients with FGF/FGFR gene aberrations who have completed at least 1 tumor assessment, the ORR was 33.3%. Of the 12 patients who had an ORR, the complete response rate was 8.3% and the partial response rate was 25%. The DCR was 91.7%.

The most common treatment-related AEs occurring in more than 20% of the patients, included hyperphosphatemia, hypercalcemia, increased ALT or AST, diarrhea and hypertriglyceridemia. Hyperphosphatemia is commonly associated with other trials targeting FGFR. It also serves as a PD biomarker of FGFR inhibition.2

We are very proud that our solid tumor drug has been granted ODD by the FDA following that for our blood cancer drug. Gunagratinib demonstrated anti-tumor activity for multiple tumor types, including cholangiocarcinoma, in patients with FGF/FGFR gene aberrations. We will rapidly advance the multi-center, multi-indication clinical trials in both the US and China in order to benefit patients early," said Jasmine Cui, PhD, the co-founder, chairwoman and CEO of InnoCare in a press release.1

1. InnoCare announces orphan drug designation of gunagratinib by US FDA for treatment of cholangiocarcinoma. News release. InnoCare. June 9, 2021. Accessed June 17, 2021. https://bit.ly/3q3uYsJ.
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. Jour. of Clin. Onc. 39, no. 15_suppl (May 20, 2021) 4092-4092. DOI: 10.1200/JCO.2021.39.15_suppl.4092