Oral abstract session: Cancers of the pancreas, small bowel, and hepatobiliary tract

The randomised, double-blind, phase III KEYNOTE-937 trial evaluated pembrolizumab vs placebo as adjuvant therapy in patients with hepatocellular carcinoma (HCC) who achieved a complete radiological response after surgical resection or local ablation. A total of 959 patients were randomised 1:1 to pembrolizumab or placebo for up to 17 cycles, or until disease recurrence, unacceptable toxicity, intercurrent illness, or withdrawal. At the third interim analysis, pembrolizumab did not significantly improve recurrence-free survival compared with placebo. As the recurrence-free survival hypothesis was not met, overall survival was not formally tested, with median overall survival not reached in either arm. No new safety signals were reported. KEYNOTE-937 did not support pembrolizumab as adjuvant therapy after curative-intent treatment of HCC.

In cholangiocarcinoma (CCA), the open-label phase I/II ReFocus study reported efficacy and safety data for lirafugratinib, a potent and selective irreversible FGFR2 inhibitor, in patients with advanced/metastatic CCA harbouring FGFR2 fusions/rearrangements, previously treated with chemotherapy and FGFR inhibitor-naïve. The reported activity was clinically relevant, with an overall response rate of 47% and a median progression-free survival of 11.3 months. The safety profile was manageable and consistent with FGFR2 inhibition, including stomatitis, nail toxicity, retinal toxicity and palmar-plantar syndrome. These results confirm clinically relevant activity of lirafugratinib in FGFR2-altered CCA.

The phase I INCB161734-101 study evaluated an investigational selective KRAS G12D inhibitor in patients with advanced/metastatic solid tumours harbouring a KRASG12D mutation, including a pancreatic ductal adenocarcinoma (PDAC) expansion cohort, as monotherapy in previously treated patients and in combination with chemotherapy (mFOLFIRINOX or gemcitabine/nab-paclitaxel), mainly in first or second line. The primary objective was safety. In monotherapy, treatment-related toxicity was manageable, with predominantly gastrointestinal adverse events such as nausea, vomiting and diarrhoea. In combination with chemotherapy, tolerability remained acceptable and did not appear to compromise chemotherapy intensity. Importantly, a promising signal of antitumour activity was reported, with an overall response rate of approximately 50% in combination therapy and approximately 35% with monotherapy in pretreated patients. Based on these findings, a global phase III trial (DAWN-303) is planned to evaluate INCB161734 in first-line metastatic PDAC harbouring a KRASG12D mutation in combination with chemotherapy.