Viagenpumatucel-L (HS-110) plus nivolumab in patients with advanced non-small cell lung cancer (NSCLC) after checkpoint inhibitor treatment failure.

Abstract

9109 Background: Viagenpumatucel-L (HS-110) is an allogeneic cellular vaccine derived from a human lung adenocarcinoma cell line transfected with the gp96-Ig fusion protein that functions as an antigen chaperone for cross presentation and dendritic cell activation. DURGA is a multi-cohort study evaluating the combination of HS-110 and anti-PD-1 monoclonal antibodies in patients with advanced NSCLC. We report on Cohort B, consisting of patients with progressive disease (PD) after receiving a minimum of 4 months of treatment (tx) with a checkpoint inhibitor (CPI) at any time prior to study entry. Methods: Patients (pts) with previously treated NSCLC received weekly HS0110 (1 X 107 cells) intradermally for 18 consecutive weeks and nivolumab IV 240 mg every 2 weeks until intolerable toxicity or PD. Tissue was tested at baseline for PD-L1 expression (≥ 1% or < 1%) and tumor infiltrating lymphocytes (TILs). TIL high was defined as > 10% CD8+ lymphocytes in the tumor stroma. The primary endpoint was objective response rate by RECIST 1.1. Results: As of the September 2018 data cut-off, 20 pts were enrolled. 18 pts (90%) had PD after both chemotherapy and CPI, and 14 (70%) had CPI as their most recent line of tx. The median number prior tx lines was 2 [range 1 to 6]. 3 pts (15%) achieved partial response and 8 pts (40%) had stable disease. Disease control rate was 55%. Progression-free survival (PFS) was 2.7 months (95% CI, 1.8 – 4.0 months) with a median follow up of 6 months. Pts experiencing injection site reactions (ISR) had improved PFS (median NR vs 2.2 months; HR 0.23, p = 0.063) compared to those without ISR. Of 3 patients with confirmed response, 2 were TIL low/PD-L1 positive, and one was TIL high/PD-L1 negative. All pts experienced at least one adverse event (AE), 80% of which were grade 1 or 2. The most common AEs were fatigue (42%), cough and dyspnea (22.6% each) and anemia (16.1%). There were no grade 5 AEs. Conclusions: The combination of HS-110 and nivolumab is well tolerated. Pts continue to be enrolled in this cohort and early data suggest that the addition of HS-110 to nivolumab may restore responsiveness after tumor progression on prior CPI therapy. Clinical trial information: NCT02439450.