Efdelikofusp alfa (CD80–IL-2v2 immunocytokine) + pembrolizumab shows 40% ORR in heavily pretreated ccRCC

Efdelikofusp alfa (GI-101A) is a CD80-IgG4 Fc–fused engineered IL-2 variant (reduced IL-2Rα affinity) designed to both antagonize CTLA-4–mediated suppression and preferentially expand CD8+ T/NK cells over Tregs; it was evaluated in KEYNOTE-B59 (GII-101-P101) Phase 1/2 dose escalation as monotherapy (Part E) or with pembrolizumab 200mg Q3W (Part F) in advanced solid tumors after progression on available therapies (total n=84; Part E n=36, Part F n=48; data cutoff December 29, 2025; NCT04977453). MTD was not reached up to 0.3mg/kg; one DLT occurred at 0.1mg/kg (grade 3 hypertension), and in the combo the most common TRAEs were pyrexia (89.6%), liver enzyme elevation (47.9%), chills (37.5%), and decreased platelets (33.3). In the ccRCC combo cohort (n=10; 70% prior IO), ORR was 40% with DCR 70% and ongoing DoR 5.5+ to 16.7+ months (median DoR not reached)—numerically above historical single-agent PD-1 activity in previously treated RCC (nivolumab ORR 21.5% in CheckMate 025), but roughly in-line with what you might expect from cabozantinib after prior IO exposure (ORR ~36% in CONTACT-03 subgroup reporting), making randomized efficacy confirmation the key next bar.