Evaluating the combined role of HHLA2 and PD-L1 as biomarkers in first-line nivolumab therapy in advanced clear cell renal cell carcinoma.

• DOI: 10.1200/jco.2025.43.5_suppl.598
• Publication Date: 2025-02-18T14:38:27Z
• Authors: Yasmin Nabil Laimon; Nourhan El Ahmar; Opeyemi Jegede; Aseman Baghari Sh...; Gordon J. Freeman; David F. McDermott; Michael B. Atkins; Sabina Signoretti; Kathleen Margaret...
• Keywords: Kidney cancer

598 Background: PD-1 directed immune checkpoint inhibitors are effective in many tumor types, including kidney cancers. HHLA2 is a negative checkpoint, generally expressed on PD-L1 clear cell renal carcinomas (ccRCC) (Bhatt, et al. 2021). Therapeutics targeting either or its inhibitory receptor KIR3DL3 Phase I trials and predictive biomarkers needed to help direct treatment. We previously reported that efficacy of nivolumab correlated with status patients cancer treated the first line setting (GU16- 260; Atkins, 2022). hypothesize expression combination may provide clinically significant biomarker for resistance blockade advanced ccRCC. Methods: cells (TC) was assessed by immunohistochemistry coupled image analysis algorithms 63 pre-treatment primary ccRCC tissues from enrolled HCRN GU16-260 trial. TC PDL-1 positivity had been evaluated this cohort (Atkins, progression-free survival (PFS) objective response rate (ORR). Results: Consistent our prior reports, did not overlap cells. identified three groups different clinical outcomes regards ORR (trend test p-value = 0.016) PFS 0.024) (Table). Patients positive (>0%) best (ORR=62.5%, median PFS=24.7 months); low (<61%) intermediate (ORR=38.5%, PFS=10.6 months) high (≥61%) worst (ORR=12.5%, PFS=3.5 months). Conclusions: Further investigation HHLA2/PD-L1 combined warranted as it be helpful identifying do respond anti-PD-1 therapy but could benefit agents HHLA2/KIR3DL3 pathway. category Number patients(63 total) (median, >0% 16 62.5% 24.7 0% & <61% (low) 39 38.5% 10.6 ≥61% (high) 8 12.5% 3.5 Trend 0.016 0.024