According to results from a phase 2 study, tinegotinib, a spectrum-selective multi-kinase inhibitor with unique binding properties to FGFR, demonstrated promising efficacy and safety among patients with advanced/metastatic cholangiocarcinoma previously treated with an FGFR inhibitor (FGFRi) and patients with non-fusion FGFR alterations.

These results were presented by lead author, Milind Javle, MD, University of Texas, MD Anderson Cancer Center, Houston, Texas, at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, California.

In this study, 48 patients with advanced/metastatic cholangiocarcinoma who previously received ≥1 line of systemic chemotherapy and had an ECOG performance status of 0 or 1 were enrolled to receive 10 mg of tinegotinib daily. Patients were broken into 4 cohorts: those with FGFR2 fusions who experienced primary progression after treatment with an FGFRi (cohort A1; n = 13), those with FGFR2 fusions who experienced progression after prior response to an FGFRi (cohort A2; n = 10), those with non-fusion FGFR alterations (cohort B; n = 12), and those with FGFR wild-type alterations (cohort C; n =13). The primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), and safety.

At the time of analysis 40 of the 45 enrolled patients were evaluable for efficacy. In cohort A1, 9.1% of patients achieved a pathological response with tumor reduction of 31.8%. In cohort A2, 37.5% of patients achieved pathological response with tumor reduction of 40.7%, 47%, and 54.6%. In cohort B, 33.3% of patients achieved a pathological response with tumor reduction of 36.5%, 48.6%, and 60.6%. No pathological response was observed in cohort C. Overall DCR was 94.7% in cohorts A1 and A2, 88.9% in cohort B, and 75% in cohort C. Median PFS was 5.26 months in cohorts A1 and A2, 5.98 months in cohort B, and 3.84 months in cohort C.

Treatment-related adverse events occurred in 93.8% of patients. The most common grade ≥ 3 treatment-related adverse events included hypertension (25%), palmar-plantar erythrodysesthesia syndrome (6.3%), diarrhea (6.3%), and stomatitis (6.3%). One patient experienced grade 4 posterior reversible encephalopathy syndrome. No grade 5 treatment-related adverse events were observed.

Dr Javle and coauthors concluded, “An ongoing randomized, controlled phase III study will evaluate the clinical efficacy, safety, and pharmacodynamic effect of tinengotinib vs physicians’ choice in subjects with FGFR2-altered refractory/relapsed [cholangiocarcinoma] after prior chemotherapy and FGFRi therapy.”

Source:

Javle MM, Mahipal A, Fonkoua LAK, et al. Efficacy and safety results of FGFR1-3 inhibitor, tinengotinib, as monotherapy in patients with advanced, metastatic cholangiocarcinoma: Results from phase II clinical trial. Presented at the 2024 ASCO Gastrointestinal Cancer Symposium; January 18-20, 2024; San Francisco, California. Abstract 434