Abstract B31: Viagenpumatucel-L (HS-110) plus nivolumab in previously treated patients with advanced non-small cell lung cancer (NSCLC)
Authors: Morgensztern Daniel , Bazhenova Lyudmila , Waqar Saiama N. , McDermott Lori , Hutchins Jeff , Harb Wael , Pennell Nathan , Cohen Roger B. 
Published: March 2020

Abstract
Background: Viagenpumatucel-L (HS-110) is an allogeneic cellular vaccine derived from a human lung adenocarcinoma (Ad) cell line transfected with the gp96-Ig fusion protein that functions as an antigen chaperone for cross-presentation and dendritic cell activation. In this context, gp96 serves as a potent immune adjuvant via Toll-like receptor 4/2 signaling, which serves to activate APCs to specialized dendritic cells as wells as cross-presentation of the gp96-chaperoned cancer testis peptide antigens (up to 725 represented) directly to MHC class I molecules for direct activation and expansion of CD8+ T-cells. DURGA is a multicohort study evaluating the combination of HS-110 and anti-PD-1 monoclonal antibodies in patients with advanced NSCLC. We report on Cohort A, which enrolled previously treated patients who have not received a checkpoint inhibitor prior to study entry.
Methods: Patients (pts) with previously treated NSCLC received 1 X 107 HS-110 cells intradermally every week for 18 weeks, and standard-of-care nivolumab IV until intolerable toxicity or tumor progression. Tissue was tested at baseline for PD-L1 expression (≥ 1% or &lt; 1%) and tumor-infiltrating lymphocytes (TILs). TIL high was defined by more than 10% CD8+ lymphocytes in the tumor stroma. The primary objectives were safety and objective response rate (ORR).
Results: As of the March 2019 enrollment cut-off, there were 46 pts enrolled into cohort A (43 Ad and 3 squamous cell carcinoma), 6 (13%) of whom were EGFR positive. 9 pts (20%) were TIL high, 13 (28%) TIL low, and 24 (52%) TIL unknown. 8 pts (17%) were PD-L1 ≥ 1%, 21 (46%) were PD-L1 &lt; 1%, and 17 (37%) were PD-L1 unknown. ORR was 22% and clinical benefit rate (objective response plus stable disease) was 48%. Median progression-free and overall survival were 1.9 and 16.9 months, respectively, with a median follow-up of 17 months. One- and 2-year survival were 48% and 30%, respectively. There were no statistically significant differences in subgroup analyses of PFS or OS based on TIL or PD-L1. In a prospectively defined secondary analysis, the presence of at least one injection site reaction (ISR) during treatment was associated with improved progression-free and overall survival: mPFS 6.1 vs. 1.6 months (HR 0.51 [95% CI 0.26, 0.97] p = 0.04), and mOS 42.1 vs. 5.9 months (HR 0.14 [95% CI 0.05, 0.36] p &lt; 0.0001). 46 (100%) pts experienced at least one adverse event (AE), of which 29 (63%) were grade 1 or 2. The most common AEs were fatigue (26%), cough and arthralgia (17% each), and decreased appetite, constipation, and diarrhea (15% each). There were 2 grade 5 AEs (pulmonary embolism and acute MI) and 1 grade 4 AE (hyponatremia), none of which were considered to be treatment related.
Conclusions: The combination of HS-110 and nivolumab appears safe and well tolerated. Efficacy results are independent of TIL and PD-L1 levels, whereas the occurrence of ISR is associated with improved progression-free and overall survival.
Citation Format: Daniel Morgensztern, Lyudmila Bazhenova, Saiama N. Waqar, Lori McDermott, Jeff Hutchins, Wael Harb, Nathan Pennell, Roger B. Cohen. Viagenpumatucel-L (HS-110) plus nivolumab in previously treated patients with advanced non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B31.