Abstract 1390P
Background
Anti-PD-1 agents are less effective in “cold tumors”, or tumors with low tumor infiltrating lymphocytes (TIL). Viagenpumatucel (HS-110), an allogeneic cellular therapy, added to anti-PD-1 may improve treatment efficacy against tumors with low TIL. This retrospective study compared the efficacy of nivolumab with and without HS-110 in tumors with low TIL.
Methods
We compared 2 separate single-arm studies: Cohort-1 (C1) is a prospective study cohort (from the DURGA trial) of previously-treated, immunotherapy naïve non-squamous NSCLC patients with ECOG 0 or 1 treated with HS-110 (intradermal injections of 1x107 HS-110 cells every week, for 18 weeks) plus nivolumab. Cohort-2 (C2) consists of real world data from the Amsterdam UMC database of similar patients who received nivolumab alone as standard of care therapy. TIL were centrally analyzed using digitalized CD8-stained pre-treatment tumor slides using dedicated software (Flagship Biosciences). Low TIL was defined as ≤10% of evaluable cells in the tumor fields. OS, ORR and disease control rate (DCR) were compared.
Results
Baseline characteristics of C1 (N=44) and C2 (N=74) were comparable, except more current smokers were in C2 (30%) vs C1 (14%). Similar ORR and DCR at 6 months (mos) were observed for C1 and C2. The OS in C1 was significantly higher than C2 (28.7 mos vs 8.9 mos, p=0.0099, HR = 0.55). In patients with low TIL, an even greater OS was seen in C1 than C2 (31.1 mos vs 4.0 mos, p=0.0053, HR = 0.28). Table: 1390P
| Cohort 1 (C1) HS-110 + Nivolumab | Cohort 2 (C2) Nivolumab | p value | Hazard Ratio | ||
| Total | N | 44 | 74 | ||
| ORR, % (95% CI) | 20.5 (9.8-35.3) | 21.6 (12.9-32.7) | |||
| 6-month DCR, % | 36 | 34 | |||
| OS, mos (95% CI) | 28.7 (10.3 – unknown) | 8.9 (5.6, 12.1) | 0.0099 | 0.55 (0.34, 0.87) | |
| TIL analysis | Evaluable pts, N | 16 | 38 | ||
| Low TIL pts, N | 12 | 30 | |||
| OS of low TIL pts, mos (95% CI) | 31.1 (15.8-unknown) | 4.0 (3.0-10.7) | 0.0053 | 0.28 (0.11,0.73) |
Conclusions
In this retrospective study, the combination of HS-110 and nivolumab was significantly improved OS in previously treated, immunotherapy naïve NSCLC pts, especially in those with low tumor CD8+ TIL levels, compared to nivolumab monotherapy. These findings are supportive of HS-110 mechanism of action.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Heat Biologics, Inc.
Funding
Heat Biologics, Inc.
Disclosure
I. Bahce: Research grant/Funding (institution): Heat Biologics, Inc. L. McDermott, J. Hutchins, J. Wolf: Full/Part-time employment: Heat Biologics, Inc. C. Caldwell, M. Argyres, B. Long: Full/Part-time employment: Flagship Biosciences. All other authors have declared no conflicts of interest.