GVAX Combination and Stereotactic Body Radiotherapy Demonstrates Clinical Promise in Borderline Resectable Pancreatic Cancer
Key Clinical Takeaways
- Design/Population: In a multicenter, phase 2 trial, 31 patients with borderline resectable pancreatic adenocarcinoma received neoadjuvant mFOLFIRINOX or gemcitabine/nab-paclitaxel (if intolerant), followed by combined immunotherapy with GVAX (GM-CSF–secreting vaccine) plus cyclophosphamide and nivolumab, and stereotactic body radiotherapy (SBRT).
- Key Outcomes: Among 18 patients treated and 14 resected, mean CD8+ T-cell density did not differ vs historical controls. Median OS was 20.4 months (median follow-up 19.5 months), with 1 pathologic complete response. Combined immunotherapy and SBRT were safe and feasible.
- Clinical Relevance: The regimen showed acceptable safety and potential immune activity but no significant increase in T-cell infiltration, highlighting the need for further studies to define immunologic and clinical benefits of neoadjuvant immunotherapy in pancreatic cancer.
According to results from a phase 2 study, the addition of GVAX, a GM-CSF-secreting vaccine that activates T-cell immunity against tumor-associated antigens plus cyclophosphamide and nivolumab (combined immunotherapy) with stereotactic body radiotherapy (SBRT) to neoadjuvant chemotherapy demonstrated promising efficacy among patients with borderline resectable pancreatic adenocarcinoma.
“Borderline resectable pancreatic ductal adenocarcinoma is treated with perioperative chemotherapy and surgical resection with or without [SBRT], but long-term survival is rare,” stated Parul Agarwal, MD, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, and coauthors. “This multicenter phase II clinical trial evaluated the safety and immune effects of GVAX/cyclophosphamide/nivolumab and SBRT on the [pancreatic ductal adenocarcinoma] tumor microenvironment.”
In this study, 31 patients were enrolled to receive either neoadjuvant mFOLFIRINOX or gemcitabine plus nab-paclitaxel (if intolerant to mFOLFIRINOX) followed by combined immunotherapy and SBRT. The primary end point was CD8-positive T-cell density in collected surgical specimens compared to historical control samples that were treated with only neoadjuvant mFOLFIRINOX and SBRT. Key secondary end points included pathological complete response and overall survival (OS).
At analysis, 18 patients received at least 1 dose of combined immunotherapy, and 14 patients underwent surgical resection. There was no difference in the mean CD8 T-cell density compared to historical controls. At a median follow-up of 19.5 months, median OS was 20.4 months and there was 1 pathological complete response. Among responders, there was a nonsignificant increase in abundance score for specific immune cell subsets compared to nonresponders.
“The addition of combined immunotherapy and SBRT was safe and feasible in this patient population, [and] no difference was observed in the mean CD8 T-cell density between study patients and historic controls,” concluded Dr Agarwal et al. “These findings support the need for better characterization of how neoadjuvant immunotherapy may shift the phenotype of the [pancreatic ductal adenocarcinoma tumor microenvironment]."
Source:
Agarwal P, Guo M, Munjal K, et al. A Phase II Study of neoadjuvant GVAX and cyclophosphamide combined with nivolumab and SBRT followed by surgery in borderline resectable pancreatic adenocarcinoma. Clin Cancer Res. Published online: August 1, 2025. doi: 10.1158/1078-0432.CCR-24-3403
