Proffered paper session (1)

In this video, Prof Dr Ivan Borbath discusses three abstracts from the Proffered Paper session held on 2 July at ESMO GI 2026: a tumour response analysis from the phase III EMERALD-3 study in embolisation-eligible hepatocellular carcinoma (eeHCC), and two early-phase studies evaluating RAS(ON)-targeted strategies in RAS/KRAS G12D-mutant metastatic pancreatic adenocarcinoma (mPDAC).^1-3

EMERALD-3 evaluated durvalumab plus tremelimumab (STRIDE), with or without lenvatinib, combined with transarterial chemoembolisation (TACE), versus TACE alone in patients with eeHCC.¹ The study met its primary endpoint, with STRIDE plus lenvatinib plus TACE significantly improving progression-free survival (PFS) per RECIST v1.1 by central review versus TACE alone (median 13.0 vs 9.8 months; HR=0.70). The current analysis additionally assessed response by modified RECIST (mRECIST), which accounts for viable, arterially enhancing tumour following locoregional therapy. Confirmed objective response rate (ORR) per mRECIST was higher with STRIDE-based regimens (65.7% with STRIDE plus lenvatinib plus TACE; 55.4% with STRIDE plus TACE) than with TACE alone (41.7%), with corresponding gains in PFS per mRECIST. Longer follow-up is needed to clarify the impact on overall survival.

In the RMC-GI-102 platform study (NCT06445062), zoldonrasib (RMC-9805; a RAS(ON) G12D selective inhibitor) combined with first-line chemotherapy in treatment-naïve RAS G12D mPDAC resulted in an ORR of 82% with modified FOLFIRINOX and 61% with gemcitabine/nab-paclitaxel with disease control rates of 96% and 90%, respectively, compared with historically reported ORRs of 23-43% with chemotherapy alone.² Adverse events were consistent with the respective chemotherapy backbones, with no new safety signals. PFS and OS data remain immature. These results support the ongoing phase III RASolute 305 trial (NCT07621718).

A chemotherapy-free doublet of zoldonrasib with the multi-selective RAS(ON) inhibitor daraxonrasib (RMC-6236) was assessed in patients who had received prior systemic therapy.³ At the recommended phase II dose, ORR was 50% in the second-line cohort and 47% in the third-line-or-later cohort, with disease control rates of 97% and 90%, respectively. Median PFS was 9.6 and 7.6 months. Safety was manageable and broadly consistent with daraxonrasib monotherapy, without clear additive toxicity. These data support further evaluation of the combination in the planned phase III RASolute 309 trial in the first-line setting.