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Phase I/II Trial of Neoadjuvant Oregovomab-based Chemoimmunotherapy Followed by Stereotactic Body Radiotherapy and Nelfinavir For Locally Advanced Pancreatic Adenocarcinoma

Lin, Chi MD, PhD*; Verma, Vivek MD; Lazenby, Audrey MD; Ly, Quan P. MD§; Berim, Lyudmyla D. MD; Schwarz, James K. MD; Madiyalakan, Madi PhD; Nicodemus, Christopher F. MD#; Hollingsworth, Michael A. PhD**; Meza, Jane L. PhD††; Are, Chandrakanth MD§; Padussis, James MD§; Grem, Jean L. MD

American Journal of Clinical Oncology: October 2019 - Volume 42 - Issue 10 - p 755–760
doi: 10.1097/COC.0000000000000599
Original Articles: Gastrointestinal
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Objective: Cancer antigen (CA)-125 influences progression, metastasis, and outcomes in pancreatic cancer. This phase I/II trial (NCT01959672) evaluated the safety, efficacy, and immunologic correlates of chemoimmunotherapy (CIT) with oregovomab (anti–CA-125), followed by stereotactic body radiotherapy (SBRT) with the radiosensitizer nelfinavir.

Materials and Methods: Following imaging, pathologic confirmation, and staging laparoscopy, subjects received three 3-week cycles of CIT (gemcitabine/leucovorin/fluorouracil/oregovomab). Thereafter, nelfinavir was delivered (1250 mg bid) for 5 weeks, with SBRT (40 Gy/5 fractions) occurring during the third week of nelfinavir. Following another cycle of CIT, pancreaticoduodenectomy was performed if resectable. Three more cycles of CIT were then delivered (total 7 cycles). In subjects with high (≥10 U/mL) CA-125, oregovomab (2 mg) was administered for 7 total doses (3 pre-SBRT, 1 between SBRT and resection, and 3 postoperatively). The enzyme-linked immunospot assay evaluated the development of CA-125–specific CD8 T-lymphocytes.

Results: The trial was prematurely closed because gemcitabine/leucovorin/fluorouracil was replaced by FOLFIRINOX and gemcitabine/nab-paclitaxel as the standard of care. Median follow-up was 13 months. Of 11 enrolled patients, 10 had high CA-125; 1 patient suffered an unexpected cardiac-related death, so 9 subjects received oregovomab. Ten received SBRT and 4 underwent resection. Overall, 6/11 patients experienced any grade ≥3 event. The median survival and time to progression were 13 and 8.6 months, respectively. Five patients had samples available for immunospot testing, of whom 2 (40%) developed CA-125–specific CD8 T-lymphocytes.

Conclusion: A combined pancreatic cancer multimodality approach using CIT and radiosensitized radiotherapy is feasible and safe; delivery of immunotherapy can lead to T-cell immunity. Re-evaluation with modern systemic paradigms is recommended.

Departments of *Radiation Oncology

Pathology

§Surgery

††Biostatistics

Internal Medicine, Division of Hematology Oncology, University of Nebraska Medical Center

**Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE

Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA

Quest PharmaTech Inc., Edmonton, AB, Canada

#AIT Strategies, Franconia, NH

A portion of this work was presented at the 2018 Annual Meeting of the American Society of Clinical Oncology.

Supported by Spore Grant Number 2 P50 CA127297-06A1.

The authors declare no conflicts of interest.

Reprints: Chi Lin, MD, PhD, Department of Radiation Oncology, Buffett Cancer Center, 505 South 45th Street, Omaha, NE 68106. E-mail: clin@unmc.edu.

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