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PPS56. A Phase II Trial Evaluating Combination Cabozantinib and Pembrolizumab in Treatment Refractory Metastatic Pancreatic Adenocarcinoma

Friday, March 6, 2026
3:40 PM - 4:10 PM MST
Location: HUB Poster Park - West Hall 1-3
Introduction: Treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) remains challenging. We have previously demonstrated programmed cell death protein 1 (PD-1)-mediated activation of the proto-oncogene MET and observed effective cytotoxicity with the combination therapy of pembrolizumab and cabozantinib in vitro and in vivo. We hypothesized that this dual therapy would result in improved progression-free survival (PFS) for patients with metastatic PDAC.


Methods: In this investigator-initiated phase II clinical trial (NCT05052723), we enrolled patients with treatment refractory metastatic PDAC to a single-arm treatment regimen of pembrolizumab 200 mg IV every 3 weeks and cabozantinib 40 mg PO daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response, complete response or partial response (PR) at one-year post treatment initiation, and one-year overall survival (OS).


Results: We successfully completed enrollment (n=21 patients) in this clinical trial. The median age was 66, 11 patients (52.4%) were female, and the majority of patients (85.7%) were white. After survival analysis, median PFS was 2.11 months (95% CI 1.87-2.52). For patients enrolled for 2nd or 3rd line therapy (n=13), median PFS was 2.11 months (95% CI 1.33-3.91) and OS was 4.02 months (95% CI 2.39-8.19). One notable PDAC patient with histology demonstrating features of undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) had PR. Imaging demonstrated stable disease until 25 months, when evidence of disease progression was identified.


Conclusions: Overall, combination therapy with cabozantinib and pembrolizumab was not superior to historical controls for treatment refractory metastatic PDAC. However, one patient with features of UCOGC had a prolonged response to therapy and remained on trial for 25 months. This suggests the unique benefit of this combination therapy for patients with UCOGC.

Learning Objectives:

  • Understand the effectiveness of cabozantinib and pembrolizumab for treatment refractory metastatic pancreatic adenocarcinoma.
  • Evaluate the benefit of dual therapy for undifferentiated carcinoma with osteoclast-like giant cells.