IPBM 2025 highlights emerging precision medicine and clinical advances in pancreatic cancer

Various clinical studies and technological strategies showing promise in applying precision medicine to pancreatic cancer—a disease with a poor prognosis—were highlighted at the International Pancreatobiliary Congress (IPBM 2025) held on Friday in Seoul.

At the event, Park Joo-kyung, a professor of gastroenterology at Samsung Medical Center, delivered a keynote lecture titled 'Drug Development in Research and Clinical Trials on Pancreatic Cancer,' reviewing the latest clinical evidence and precision treatment strategies.

“Pancreatic cancer is often detected at an advanced stage and has an extremely poor prognosis,” said Park. “The global incidence is expected to increase steadily from 2018 to 2040, and Asia is emerging as a center for clinical research, currently hosting 57 percent of the world’s pancreatic cancer clinical trials.”

She also highlighted the practical challenges of drug development. “De novo drug discovery and the development of entirely new mechanisms take an average of 10 to 17 years, with a low probability of success and high risk of failure,” said Park. “While advances in treatment strategies are being made, many challenges remain.”

Park introduced two studies as representative of the latest clinical developments. One is the phase 3 NAPOLI-3 trial, which demonstrated the efficacy of NALIRIFOX therapy using Onyvide (nanoliposomal irinotecan). The other is the phase 2 PASS-01 study, which analyzed differences in treatment response based on molecular subtypes (classical vs. basal-like) and explored the potential for precision therapy using patient-derived organoids (PDX).

NAPOLI-3 is a phase 3 study comparing the NALIRIFOX regimen (nanoliposomal irinotecan, oxaliplatin, 5-fluorouracil, and leucovorin) to conventional gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel, brand name Abraxane) in the first-line treatment setting.

A total of 770 patients were enrolled, with a median overall survival (OS) of 11.1 months in the NALIRIFOX arm (383 patients) compared to 9.2 months in the gemcitabine plus nab-paclitaxel arm (387 patients), demonstrating a significant survival benefit (HR = 0.83). Progression-free survival (PFS) was also significantly prolonged.

“The NAPOLI-3 study has a clinically attractive design, but implementing this combination therapy in real-world settings in Korea is challenging,” she said. “Although NAPOLI-3 provides high-level evidence, it still highlights a gap between clinical research and actual practice.”

Referring to the PASS-01 study, Park noted that the molecular subtypes of pancreatic cancer—classical and basal-like—are well established as prognostic factors, but their use as predictive markers remains in the early stages. The study presented preliminary data at the American Society of Clinical Oncology (ASCO) 2024, with final results expected in 2026.

In the PASS-01 study, patient-derived organoids and transcriptome profiling were used to classify patient subtypes and guide first-line chemotherapy. Patients with the classical subtype received mFOLFIRINOX, while those with the basal-like subtype were treated with gemcitabine plus nab-paclitaxel. Response rates and survival outcomes were then analyzed.

An interim analysis showed a median progression-free survival of 5.7 months for the classical subtype and 2.7 months for the basal-like subtype. However, “single-cell transcriptome analysis revealed that basal-like cells accounted for more than 30 percent in some cases, indicating that subtype classification does not always align with actual clinical response,” Park noted. She emphasized that “more refined criteria are needed to apply molecular subtypes effectively in clinical treatment.”

Park also discussed the development of targeted therapies for KRAS mutations, the most common genetic abnormality in pancreatic cancer. Approximately 90 to 95 percent of pancreatic cancer patients have KRAS mutations, with G12D and G12V being the most prevalent. Recently, inhibitors targeting the G12C mutation have been developed, and research is now expanding to pan-KRAS inhibitors.

For example, Revolution Medicines' pan-KRAS inhibitor has shown promising results in pancreatic cancer, with an objective response rate (ORR) of 30 percent and a disease control rate (DCR) of 80 percent, she said.

Park explained that in patients with wild-type KRAS, gene abnormalities such as NTRK, ROS1, and FGFR2 are typically mutually exclusive and require distinct targeted approaches. For those without KRAS mutations, she emphasized the importance of screening for fusion genes or DNA repair defects such as homologous recombination deficiency (HRD) and microsatellite instability-high (MSI-H).

Park noted that in the field of antibody-drug conjugates (ADCs), new therapies targeting HER3 expression are showing responses in some pancreatic cancer patients. In a pan-cancer ADC trial involving patients with high HER3 expression, two pancreatic cancer patients demonstrated an overall survival (OS) of 12.4 months.

Dr. Park explained that ADC therapies targeting HER3, TROP2, CEACAM5, and other markers are currently under investigation in biliary tract cancers, with some being extended to pancreatic cancer. While HER3 positivity is relatively low in pancreatic cancer, she noted that there is potential to explore these therapies based on patient-specific biomarkers.

“In the past 25 years, only a limited number of therapies have demonstrated a survival benefit in treating metastatic pancreatic cancer, and most clinical trials have not adequately represented elderly or vulnerable populations,” said Park. “Looking ahead, new technologies such as patient-derived xenograft (PDX) models, antibody-drug conjugates (ADCs), and pan-KRAS inhibitors are expected to be introduced, but their clinical applicability still requires further investigation.”

“Pancreatic cancer is extremely heterogeneous and characterized by highly complex tumor biology, which limits the effectiveness of single-targeted therapies,” Park concluded, adding that “precision medicine approaches are no longer optional—they are a necessity.”