Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Innate and adaptive immunotherapy: An orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T cell therapy in patients with third line or greater metastatic pancreatic cancer.
Gastrointestinal (Noncolorectal) Cancer
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e15787)
Author(s): Tara Elisabeth Seery, Mira Kistler, Leonard S. Sender, John H. Lee, Arvind Manohar Shinde, Anand Annamalai, Patrick Soon-Shiong; Chan Soon Shiong Institute for Medicine, Laguna Hills, CA; Chan Soon Shiong Institute of Medicine, El Segundo, CA; Chan Soon Shiong Institute for Medicine, El Segundo, CA; Nantkwest, Culver City, CA; St. Vincent Medical Center, Los Angeles, CA; St. Vincent's Medical Center, Los Angeles, CA
Background: Pancreatic cancer has multiple mechanisms to prevent immune recognition that lead to the creation of an immune suppressive tumor microenvironment. We hypothesize that sustained response against pancreatic cancer requires a coordinated approach that: 1. reverses the immune-suppressive tumor microenvironment, 2. induces immunogenic tumor cell death and 3. reengages NK and T-cell tumor response against a 4. cascade of tumor antigens. To test this hypothesis, we have developed a temporospatial approach that combines metronomic low-dose chemotherapy, SBRT, cryopreserved allogeneic NK cells, yeast and adenoviral tumor-associated antigen vaccines, an IL-15RαFc superagonist, and checkpoint inhibition. Methods: A phase 1b trial in patients with recurrent metastatic pancreatic cancer was initiated. Treatment occurred in 3-week cycles of low-dose chemotherapy (aldoxorubicin, cyclophosphamide, oxaliplatin, nab-paclitaxel, 5-FU/L), antiangiogenic therapy (bevacizumab), SBRT, allogeneic CD16 NK-92 cells (haNK), IL-15RαFc (N-803), adenoviral CEA vaccine, yeast Ras vaccine, and an IgG1 PD-L1 inhibitor, avelumab. The primary endpoint is incidence of treatment-related adverse events (TRAEs). Secondary endpoints include ORR, DCR, PFS, and OS. Results: 12 subjects with 3rd-line or greater metastatic pancreatic cancer were treated. All treatment was administered in an outpatient setting. AEs were primarily hematologic and managed by planned chemo dose reduction. Grade ≥3 TRAEs were observed in 9 out of 12 subjects, predominately chemotherapy-related neutropenia. 9 out of 12 subjects (75%) had a best response of stable disease (≥ 8 weeks). Median PFS is 7.1 months (4.4 – 8.8) and median OS is 8.2 months (5.7 – 9.7) with 1 subject continuing treatment. Conclusions: These preliminary data suggest that low-dose chemo-radiation combined with innate and adaptive immunotherapy can be administered safely in an outpatient setting. Preliminary OS of 8.2 months is encouraging for this heavily-pretreated population. Clinical trial information: NCT03586869