Abstract C002: A pilot study to assess the safety, tolerability, and tumor responses with lenvatinib plus pembrolizumab in patients with advanced pancreatic ductal adenocarcinoma in second-line or later of treatment

Abstract Introduction Lenvatinib plus PD-1 inhibition substantially decreases tumor-associated macrophages and increases infiltration of CD8+ T-cells in mouse tumor models, enhancing anti- tumor activity, thus providing the background rationale to explore the clinical response and the safety of the combination of lenvatinib plus pembrolizumab in patients with pancreatic cancer. Methods Patients with metastatic pancreatic adenocarcinoma with disease progression on ≥ 1 line of systemic therapy were eligible for screening. Eligible patients received therapy on a 42 day cycle, receiving fixed doses of 400mg of pembrolizumab on day 1 and 20mg of lenvatinib daily. Blood and tumor tissue were collected to evaluate molecular determinants of response and changes in the tumor’s T-cell composition. Results Fifteen patients received treatment on protocol, with a median of 1 cycle of treatment. Of these 15 patients, 5 were female and 10 were male; 12 enrolled at a performance status of 0 and 3 at a 1; 10 had one prior line of therapy in the metastatic setting and 5 had 2 lines. Currently, 1 patient remains on protocol after 3 cycles of therapy; 3 other patients who had disease progression on protocol remain alive at the time of this submission and are on other treatments. While no tumor responses were observed on therapy, 7 patients had stable disease and remained on treatment beyond 1 cycle of therapy. In 3 of these 7 patients, CA 19-9 trend was consistent with cancer control (1 additional patient was a nonproducer). The disease control rate was 47% and the median progression free survival was 10 weeks [95% CI, 6.3 – 11.7]. Median overall survival was 19.8 weeks [95% CI, 13.5 – 26.1]. All 14 patients who discontinued therapy did so due to disease progression; none stopped therapy due to treatment related toxicity. Four patients had either lenvatinib dose delays or reductions per protocol due to toxicity; no patients had dose delays/modifications to the pembrolizumab. No unexpected adverse events were experienced. The most frequently occurring toxicities of any grade were fatigue (8), hypertension (7), proteinuria (6), nausea (4), hypothyroidism (4), mucositis (4), and hyponatremia (4). There was one occurrence of each of the following serious adverse events, with noted CTCAE grade (Gr) and attribution to therapy: sepsis (Gr3, unrelated), immune mediated endocrinopathy (Gr3, possibly related), hypotension (Gr3, possibly related), fatigue (Gr3, unrelated), lung infection (Gr3, probably related), enterocolitis (Gr3, probably related), fever (Gr3, possibly related). There were no grade 4 or 5 events. Conclusions The combination of pembrolizumab with lenvatinib demonstrated pancreatic cancer control which, while modest, is appreciated in this later line of therapy where few treatment options exist. These benefits were achieved while being a safe and manageable treatment for patients. Blood and tissue data will offer further insights into tumor responses, and combination of this therapy with chemotherapy and in an earlier line of treatment is being explored. Citation Format: Brandon G Smaglo, Ryan Sun, Shubham Pant, Michael S Lee, Dan Zhao, Phat H Le, Milind Javle, Jason A Willis, Christine Parseghian, Manoop Bhutani, Saman Chishty, Stacy Diao, Michael W Leung, Ryan W Huey, Maria Pia Morelli, Michael J Overman, Robert A Wolff. A pilot study to assess the safety, tolerability, and tumor responses with lenvatinib plus pembrolizumab in patients with advanced pancreatic ductal adenocarcinoma in second-line or later of treatment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C002.