Promising efficacy data for next-gen FGFR inhibitor tinengotinib in CCA

Presented by

Dr Milind Javle, MD Anderson Cancer Center, TX, USA

Conference

ASCO GI 2024

Trial

Phase 2

Doi
https://doi.org/10.55788/c63717a3

The next-generation fibroblast growth factor receptor (FGFR) inhibitor tinengotinib delivered encouraging efficacy results in patients with advanced, metastatic cholangiocarcinoma (CCA) in a phase 2 study. The agent was well tolerated, and a phase 3 trial has been initiated to further investigate the potential of tinengotinib in the CCA population.

Dr Milind Javle (MD Anderson Cancer Center, TX, USA) presented the findings of an interim analysis of a phase 2 study (NCT04919642) investigating tinengotinib, a novel, multi-kinase inhibitor of FGFR [1]. The trial enrolled 55 patients with advanced, metastatic CCA, who were divided into 4 cohorts:

A1: patients with FGFR2 fusions who had progressed on prior FGFR inhibitor therapy (n=18);
A2: patients with FGFR2 fusions who had a response on prior treatment with FGFR inhibitor but acquired resistance, and thus subsequently discontinued due to progressive disease (n=11);
B: patients with other, non-fusion FGFR alterations (n=13); and
C: patients with FGFR wildtype (n=13).

All participants received 10 mg tinengotinib once daily, until disease progression, unacceptable toxicity, or another discontinuation criterion was met. The primary endpoint was overall response rate (ORR).

In the combined cohorts A1, A2, and B, the ORR was 26.3% and the disease control rate was 94.7%. In participants with acquired resistance to prior FGFR inhibitors the ORR appeared to be highest, at 40%. Next, in participants with other FGFR alterations, the ORR was 30.8%. “The median progression-free survival was 5.4 months in cohort A, 8.1 months in cohort B, and 3.8 months in cohort C,” added Dr Javle.

The safety profile of tinengotinib was favourable, with no reported grade 4 or 5 treatment-emergent adverse events (TEAEs). Dose interruptions, dose reductions, and treatment discontinuations due to TEAEs occurred in 62%, 31%, and 13% of the participants, respectively. Hypertension (62%), stomatitis (40%), and diarrhoea (40%) were the most common TEAEs.

“Tinengotinib is a next-generation FGFR inhibitor with promising efficacy in patients with CCA and FGFR alterations who are refractory to current FGFR-targeted therapies,” decided Dr Javle. “A phase 3 trial (FIRST-308; NCT05948475) has been launched to further evaluate this agent.”

Javle M, et al. Efficacy and safety results of FGFR1-3 inhibitor, tinengotinib, as monotherapy in patients with advanced, metastatic cholangiocarcinoma: interim results from phase II clinical trial. Abstract 434, ASCO Gastrointestinal Cancers Symposium 2024, 18–20 January, San Francisco, CA, USA.

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