Efficacy and Safety of Tinengotinib in Patients With Advanced Refractory/Relapsed CCA Who Previously Received an FGFR Inhibitor

Investigators pooled data from 3 trials to evaluate tinengotinib in patients with advanced, refractory/relapsed cholangiocarcinoma who previously received an FGFR inhibitor.

FGFR inhibitors play an important role in the management of patients with cholangiocarcinoma (CCA) harboring FGFR alterations after patients have undergone chemotherapy. Tinengotinib was identified as a novel FGFR inhibitor with high potency to a variety of FGFR2 kinase domain mutations and has shown promising clinical results in patients with CCA who have progressed on a prior FGFR inhibitor. At the 2023 ESMO Congress in Madrid, Spain, Meredith S. Pelster, MD, presented pooled data from 3 trials of tinengotinib in patients with CCA.

The pooled analysis consisted of data from phase 1 (NCT03654547), phase 1b/2 (NCT04742959), and phase 2 (NCT04919642) studies of tinengotinib in patients with advanced CCA. Patients received tinengotinib orally once or twice daily for 28 days per cycle. Patients were eligible if they were ≥18 years; had advanced/metastatic or surgically unresectable CCA and received ≥1 line of prior systemic chemotherapy; had ≥1 measurable lesion as defined by RECIST version 1.1 criteria; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. A pooled analysis of treatment-related adverse events (TRAEs), overall response rates (ORRs), disease control rates (DCRs), and median progression-free survival (PFS) was conducted in a stratified CCA population.

FGFR inhibitors play an important role in the management of patients with cholangiocarcinoma (CCA) harboring FGFR alterations after patients have undergone chemotherapy.

The full analysis set included 89 patients from the 3 different clinical trials: phase 1 (n=14), phase 1b/2 (n=26), and phase 2 (n=49). Median age was 61 years (range, 24-81); 60% were women; and 100% of patients had ≥1 prior therapy, including 47% of patients with prior FGFR inhibition. The majority of TRAEs were grade 1/2 and were reversible and manageable. The most common TRAEs (≥20%) were hypertension (all grades, 53%; grade 3, 23%), stomatitis (all grades, 35%; grade 3, 5%), diarrhea (all grades, 30%; grade 3, 3%), and palmar-plantar erythrodysesthesia (all grades, 25%; grade 3, 5%). In 41 patients with FGFR2 altered CCA, the ORR and DCR were 29% and 90%, respectively. The 36 patients who acquired resistance to prior FGFR inhibition had an ORR of 31% and a DCR of 92%. The 16 patients who developed FGFR2 kinase domain mutations detected by liquid biopsy at baseline had an ORR of 44% and a DCR of 94%. The median PFS for FGFR2 altered CCA was 5.98 months (95% confidence interval [CI], 5.26-9.10); for patients previously receiving an FGFR inhibitor with refractory/relapsed CCA, the median PFS was 6.01 months (95% CI, 5.26-9.10); and in patients with CCA with FGFR2 kinase domain mutations, median PFS was 6.90 months (95% CI, 2.86-13.44).

The results of this pooled analysis suggest that tinengotinib has a manageable toxicity profile in patients with CCA. Tinengotinib was associated with clinical benefit in patients with FGFR altered CCA with acquired resistance to prior FGFR inhibition. To further evaluate the safety and efficacy of tinengotinib in this patient population, a global phase 3 clinical trial is studying tinengotinib versus physician’s choice (NCT05948475).

Source:

Javle M, Liao C-YA, Mahipal A, et al. Tinengotinib in patients with advanced FGFR inhibitor refractory/relapsed cholangiocarcinoma. Presented at: ESMO Congress 2023, October 20-24, 2023; Madrid, Spain.