Mini Oral Session 3

Dr Willem Lybaert, a medical oncologist at VITAZ Sint-Niklaas and University Hospital Antwerp, provided a comprehensive review of pivotal studies presented during the Mini Oral Session 3 at the ESMO GI Congress.

In the TOPAZ-1 study, the primary analysis revealed that the combination of durvalumab with gemcitabine and cisplatin (GC) significantly improved OS compared to the placebo with GC in patients with advanced BTC. Following a median follow-up duration of approximately 41 months, durvalumab combined with GC continued to demonstrate a clinically meaningful long-term survival benefit, particularly in patients who achieved disease control. Participants receiving durvalumab with GC were more likely to be classified as extended long-term survivors than those receiving placebo with GC. Furthermore, durvalumab with GC maintained a tolerable safety profile. These updated survival and safety data further endorse durvalumab combined with GC as a standard of care treatment for patients with locally advanced or metastatic biliary tract cancer.

PD-L1 biomarker analysis was conducted in two studies, specifically the RATIONALE-305 and RATIONALE-306 trials. These studies investigated the efficacy of tislelizumab combined with chemotherapy in patients with HER2-negative advanced or GC/GEJC and in those with locally advanced unresectable or metastatic ESCC, respectively. The concordance between the PD-L1 Tumour Area Proportion (TAP) score and the Combined Positive Score (CPS) at matched thresholds (1% vs. 1%, 5% vs. 5%, 10% vs. 10%) was evaluated. Both the TAP score and CPS were found to be reliable metrics for measuring PD-L1 expression, and demonstrated substantial concordance among the patient cohorts enrolled in the studies.

A primary analysis of the OPTIMIZE-1 phase Ib/II study, which investigated the CD40 agonist mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma was presented. CD40 agonism represents a promising therapeutic approach in pancreatic cancer, offering a mechanism to disrupt the tumour stroma and potentiate anti-tumour immune responses. The study successfully met its primary endpoint of ORR and an unprecedented DoR was observed which was associated with a clinically meaningful survival benefit. The safety profile was manageable. These encouraging results support the continued development of mitazalimab in a randomised phase III study.

Another phase I study evaluated the anti-claudin 18.2 ADC IBI343, conjugated to exatecan, in patients with solid tumours and G/GEJ AC. This study included both dose escalation and expansion phases within a pretreated patient population. IBI343 was well tolerated, exhibiting low gastrointestinal toxicity and no cases of interstitial lung disease. Encouraging efficacy was observed in patients with moderate to high CLDN18.2 expression in GC/GEJC. A phase III trial of IBI343 at a dose of 6 mg/kg is being initiated.