Infigratinib Receives Breakthrough Therapy Designation in China for Gastric Cancer

China’s National Medical Products Administration (NMPA) has granted a breakthrough therapy designation to infigratinib (Febseltiq) for the treatment of patients with gastric cancer.¹

The designation was supported by topline data from a phase 2a trial (NCT05019794), which showed that pretreated patients with locally advanced or metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma harboring FGFR2 gene amplification experienced an overall response rate (ORR) of 25.0% (n = 20). The median duration of response (DOR) was 3.8 months.

“Gastric cancer impacts a disproportionately high number of patients in China,” Yizhe Wang, PhD, chief executive officer of LianBio, stated in a news release. “Patients whose disease has progressed on existing treatment options face a poor prognosis today. The topline data from this proof-of-concept trial suggest infigratinib has the potential to provide meaningful clinical benefit in third-line or later gastric cancer. We look forward to further investigating the efficacy and safety of infigratinib in this patient population in a phase 2 study designed to support registration in China that we plan to initiate next year.”

Infigratinib is an oral, adenosine triphosphate–competitive, FGFR TKI designed to target the FGFR protein and inhibit downstream activity. In May 2021, the FDA granted accelerated approval to infigratinib for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.²

However, in October 2022, LianBio reported that its partner, BridgeBio Pharma, informed the company that Helsinn Healthcare SA was permanently discontinuing distribution of the drug and anticipated requesting withdrawal of the new drug application in the United States due to business reasons.³

In December 2022, the European marketing authorization application for infigratinib was withdrawn by Helsinn Birex Pharmaceuticals for the treatment of patients with advanced cholangiocarcinoma harboring FGFR2 fusions or rearrangements.⁴

The multicenter, open-label, single-arm, phase 2a proof-of-concept study enrolled patients with FGFR2-amplified locally advanced or metastatic gastric cancer or GEJ adenocarcinoma, and those with other advanced solid tumors harboring FGFR alterations, who received at least 2 prior lines of treatment. Patients were also required to have measurable disease per RECIST v1.1 criteria and an ECOG performance status of 0 or 1.⁵

Key exclusion criteria included a history of other primary malignancies with 3 years except for adequately treated in situ carcinoma of the cervix, non-melanoma carcinoma, or any other curatively treated malignancy that was not expected to require treatment for recurrence during the study; prior treatment with a mitogen-activated protein kinase or selective FGFR inhibitor; or symptomatic central nervous system metastases.

All patients were treated with 125 mg of oral infigratinib per day on a 3-weeks-on/1-week-off schedule.

ORR served as the trial’s primary end point. Secondary end points included DOR, disease control rate, best overall response, progression-free survival, overall survival, and safety.

In the phase 2a portion of the trial, 57.1% of patients received 2 prior lines of therapy, 33.3% were given 3 prior lines of therapy, and 9.5% had more than 3 prior lines of therapy.¹

Regarding safety, the most common any-grade treatment-emergent adverse effects reported in at least 20% of patients included hyperphosphatemia, anemia, increased alanine aminotransferase, increased aspartate aminotransferase, decreased white blood cell count, decreased neutrophil count, diarrhea, constipation, palmar-plantar erythrodysesthesia, increased lipase, increased blood alkaline phosphatase, and increased blood bilirubin.

References

1. LianBio announces topline results from phase 2a proof of concept trial evaluating infigratinib in patients with gastric cancer & receipt of breakthrough therapy designation in China. News release. LianBio. June 6, 2023. Accessed June 15, 2023. https://investors.lianbio.com/news-releases/
2. FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. News release. FDA. May 28, 2021. Accessed June 15, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/
3. United States Securities And Exchange Commission: form 8-K. Securities And Exchange Commission. October 12, 2022. Accessed June 15, 2022. https://www.sec.gov/ix?doc=/Archives/edgar/data/1831283/
4. Withdrawal of application for the EMA marketing authorization of infigratinib. News release. ESMO. December 1, 2022. Accessed June 15, 2023. https://www.esmo.org/oncology-news/withdrawal-of-application-for-the-ema-marketing-authorisation-of-infigratinib
5. Infigratinib in subjects with GC or GEJ with FGFR2 amplification or other solid tumors with other FGFR alterations (FGFR). ClinicalTrials.gov. Updated June 27, 2022. Accessed June 15, 2023. https://clinicaltrials.gov/ct2/show/NCT05019794