Ruijin Hospital Shen Baiyong Team Pancreatic Cancer Triplet Therapy Study Presented at ESMO Annual Meeting

Background

Pancreatic cancer is known as the "king of cancers" due to its aggressive nature, with a global five-year survival rate of approximately 10%. Traditionally, only a limited proportion of patients present with disease amenable to immediate surgery, and recurrence rates remain high even after resection and adjuvant chemotherapy. KRAS mutations are present in 80 to 90 percent of pancreatic ductal adenocarcinomas, with the G12D variant accounting for about 40 percent of these cases. Standard neoadjuvant chemotherapy has historically achieved objective response rates of around 30 percent.

At the 2026 European Society for Medical Oncology (ESMO) Annual Meeting, the team from Ruijin Hospital led by Prof. Shen Baiyong (also referred to as Baiyong Shen) presented preliminary results from a phase II study (abstract LBA85) in rapid oral format. This represents the world's first clinical exploration of a chemotherapy plus targeted therapy plus immunotherapy triplet regimen used in the perioperative setting for KRAS G12D-mutant pancreatic cancer. The team has proposed a new treatment paradigm of immune assessment-guided balanced therapy combining these modalities.

What was achieved

The investigator-initiated phase II study enrolled 60 patients with resectable or borderline resectable KRAS G12D-mutant pancreatic cancer. Patients were divided into two cohorts of 30 each. One cohort received the Chinese-developed KRAS G12D inhibitor HRS-4642 (from Jiangsu Hengrui Pharmaceuticals) combined with chemotherapy (gemcitabine and nab-paclitaxel). The second cohort received the same regimen plus the immunotherapy agent adebrelimab. All patients received four cycles of neoadjuvant therapy, underwent surgery where appropriate, and then completed four cycles of adjuvant therapy.

Preliminary results showed an objective response rate of 87 percent (reported as 88 percent among 25 evaluable patients in associated ESMO materials), compared with the historical approximately 30 percent for neoadjuvant chemotherapy. The disease control rate was 100 percent. Tumor shrinkage was observed in all evaluable patients, with significant declines in the tumor marker CA19-9 in the majority. Among patients proceeding to surgery, the R0 resection rate was 100 percent. Major pathological response was reported in approximately 17-19 percent of cases, including isolated pathological complete responses. Six-month event-free survival was 96 percent in the triplet cohort and 87 percent in the doublet cohort.

The addition of immunotherapy further improved immune cell function. Treatment-related adverse events occurred in 93.3 percent of patients, with grade 3/4 events in 46.7 percent and no treatment-related deaths. A phase III multicenter randomized controlled trial led by Ruijin Hospital is advancing through procedures and is expected to launch soon to confirm longer-term clinical value.

How it works

The triplet regimen combines agents that target different aspects of tumor biology. HRS-4642 specifically inhibits the KRAS G12D mutant protein that drives growth in these cancers. Gemcitabine and nab-paclitaxel are standard chemotherapy drugs that damage the DNA or disrupt division of rapidly proliferating cancer cells. Adebrelimab is an anti-PD-L1 immunotherapy that helps activate the patient's own immune cells to recognize and attack the tumor. The regimen is guided by immune assessment to achieve balanced integration of the three components for potential synergy.

In practice, patients receive four cycles of the systemic therapy before surgery (neoadjuvant phase). This aims to shrink the tumor, improve resectability, and increase the chance of complete surgical removal. Surgeons then perform resection of the pancreatic tumor with the goal of achieving R0 margins, meaning no detectable cancer cells at the edges of the removed tissue. Following surgery and recovery, patients receive four additional cycles of therapy (adjuvant phase) to address any remaining microscopic disease and reduce the risk of recurrence. This full perioperative approach integrates drug treatment throughout the surgical period rather than relying on chemotherapy alone.

What it means for international patients

These preliminary results from the phase II study suggest potential improvements in tumor response and surgical outcomes for patients with KRAS G12D-mutant resectable or borderline resectable pancreatic cancer. The six-month event-free survival signals are described as encouraging, although longer-term overall survival and disease-free survival data require confirmation from the planned larger multicenter randomized phase III trial. Applicability is limited to patients with confirmed KRAS G12D mutation who meet specific eligibility criteria such as resectability status and performance level.

Ruijin Hospital maintains an International Medical Department that provides services for overseas patients, including English-language support, interpretation in multiple languages, VIP facilities, and direct billing arrangements with various international insurance providers. It has been recognized as a Shanghai international medical tourism pilot unit. International patients interested in this approach or related care should contact the hospital directly to confirm current eligibility, requirements for genetic testing, multidisciplinary evaluation, and availability under clinical protocols or standard practice. Individual outcomes cannot be guaranteed and must be assessed on a case-by-case basis.

About the hospital

Ruijin Hospital is a Grade 3, Class A tertiary general teaching hospital located in the Huangpu District of Shanghai. Founded in 1907 (originally as Guangci Hospital or Sainte-Marie Hospital), it is affiliated with Shanghai Jiao Tong University School of Medicine. The hospital has approximately 2,700 staffed beds and employs thousands of medical professionals, including multiple academicians of the Chinese Academy of Sciences and Engineering.

It is particularly recognized for its Pancreatic Disease Center, described across reports as one of the world's largest dedicated platforms for the condition. The center handles a high annual volume of pancreatic surgeries (approaching 4,000 cases per year in some reports), with a strong emphasis on robotic-assisted minimally invasive techniques (thousands of cases completed, ranking among global leaders). It promotes multidisciplinary management across screening, surgery, targeted and immune therapies, and long-term follow-up. The hospital also operates a dedicated International Medical Center with coordinated care, expedited services, and support for foreign patients.