Phase 2 trial of durvalumab and radiation revaccination in patients with metastatic adenocarcinoma of the pancreas who have progressed through first-line chemotherapy.

Abstract

TPS461 Background: Emerging data suggest that immunotherapy combined with radiation therapy (RT) can lead to robust anti-tumor immune responses within many tumor types. While not highly immunogenic, pancreatic cancer has been shown to respond to immunotherapy especially when combined with RT. Our research hypothesis is that the combination of RT and immunotherapy (durvalumab) is well tolerated and stimulates a clinically significant pancreas-cancer specific immune response. Methods: Metastatic pancreatic cancer patients who have progressed through first-line chemotherapy will receive durvalumab every 4 weeks and will concurrently receive 24 Gy in 3 daily fractions to one pancreatic cancer lesion during week 3 followed by 24 Gy in 3 daily fractions to a second lesion during week 5. Durvalumab will continue until disease progression or unacceptable toxicity. Two lesions (instead of only one) will receive RT sequentially because of the potential for radiation “revaccination” to generate a more robust anti-tumor immune response, as our group previously published from a pancreas cancer mouse model. The primary objective is to evaluate whether the combination of RT and durvalumab can improve median PFS compared to chemotherapy historical control data. Secondary endpoints include evaluation of toxicity, overall survival, overall response rate, clinical benefit rate, and time to in-field progression. We will evaluate whether there is any correlation between durvalumab plus RT and levels of CD8 T cells, regulatory T cells, or myeloid derived suppressor cells in the peripheral blood at various intervals before, during, and after therapy. We will use a 1-sided test with a 5% significance level (a) to test the uni-directional hypothesis that the median PFS is prolonged from 3 to 4.5 months by combining RT with durvalumab. With a statistical power (1-b) of the study of 80%, we estimate an accrual time of 26 months for a total sample size of 39 patients. A positive signal from this trial that RT revaccination with concurrent checkpoint inhibitor is effective and well tolerated would provide support for a randomized trial. Clinical trial information: NCT03490760.