Abstract A099: Preliminary pharmacodynamic characterization in patients with platinum-resistant ovarian cancer treated with nemvaleukin in combination with pembrolizumab
Authors: Winer Ira , Vaishampayan Ulka N. , Gilbert Lucy , Gandhi Shipra , Velcheti Vamsidhar , Dalal Rita , Du Yangchun , Donatelli Sarah , Panchabhai Sonali , Strauss James F. , Piha-Paul Sarina 
Published: March 2024

Abstract
Introduction: Platinum-resistant ovarian cancer (PROC) is associated with poor treatment outcomes, leaving an unmet need for effective therapy. Nemvaleukin alfa selectively binds to the intermediate-affinity IL-2 receptor, activating and expanding immune effector cells with minimal expansion of T regulatory cells (Tregs). The ARTISTRY-1 trial has shown clinical activity of nemvaleukin in combination with pembrolizumab in PROC, which is being further tested in the Phase 3 ARTISTRY-7 trial. Here, we characterize pharmacodynamic (PD) effects in blood in PROC patients treated with nemvaleukin in combination with pembrolizumab. Methods: Whole blood samples were collected from patients with ovarian cancer at baseline and during treatment in the ARTISTRY-1 study (NCT02799095) and were analyzed by flow cytometry to examine immune cell modulation. Patients received nemvaleukin 3μg/kg Q5D daily + pembrolizumab 200 mg in 21-day (D) cycles and were assessed at baseline (Pre-Rx C1D1) and longitudinally (C1D8 and C2D8). Immunophenotyping of whole blood (absolute counts, cells/μL) was conducted for T cells, B cells, natural killer (NK) cells, Tregs, and subtypes. Best overall response is as of 27 Mar 2023 with scans occurring every 6 (±1) weeks. Results: Patients included N=14 at baseline and N=11 for longitudinal assessments. Higher baseline numbers of CD4 central memory cells predicted longer PFS for the nemvaleukin+pembrolizumab combination (CD4 low: mPFS=9.4 wks vs CD4 high: mPFS=54.8 wks). Higher baseline numbers of B cells and memory T cells (CD8 central and CD4 effector) also showed a trend towards longer PFS. Longitudinal analysis showed that during treatment there was a 6-fold expansion of NK cells and a 2.7-fold expansion of CD8 cells, with minimal change in the number of Tregs. NK cell ratio with cutoff of 1.1 at C2D8/C1D8 correlated with response and trended towards longer PFS.Conclusion: These preliminary PD data suggest immune activation after treatment in PROC, therefore warranting further study of nemvaleukin combined with anti-PD-1/PD-L1 agents in PROC. Further validation of the promising PD data at the tumor site using paired biopsies is being conducted in the ongoing ARTISTRY-3 trial in PROC patients treated with nemvaleukin.
Citation Format: Ira Winer, Ulka N. Vaishampayan, Lucy Gilbert, Shipra Gandhi, Vamsidhar Velcheti, Rita Dalal, Yangchun Du, Sarah Donatelli, Sonali Panchabhai, James F. Strauss, Sarina Piha-Paul. Preliminary pharmacodynamic characterization in patients with platinum-resistant ovarian cancer treated with nemvaleukin in combination with pembrolizumab [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A099.