1883MO MEDI5752 (volrustomig), a novel PD-1/CTLA-4 bispecific antibody, in the first-line (1L) treatment of 65 patients (pts) with advanced clear cell renal cell carcinoma (aRCC)

PD-1/CTLA-4 inhibition has improved survival in aRCC but maximizing the potential benefit of CTLA-4 inhibition is limited by toxicity. MEDI5752 (volrustomig) is designed to fully inhibit PD-1 while preferentially inhibiting CTLA-4 on activated PD-1+ T cells. This first-time-in-human trial showed encouraging activity with volrustomig 1500 mg in 1L aRCC. We present data from the 750 mg and 500 mg cohorts (M750 and M500). Treatment-naïve pts with aRCC received M750 mg or M500 mg every 3 weeks until disease progression or unacceptable toxicity. The primary objective was objective response rate (ORR). In M750 (n=32)/M500 (n=33), 75.0/63.6% had IMDC I/P risk. Median duration of follow-up in M750/M500 was 15.9 (range, 2.2-20.4)/8.6 (1.6-14.7) months. ORR was similar in M750/M500 (46.9%/45.5%), with higher CR rate/DCR and longer mPFS in M750 (Table). The median duration of response (DOR) was 13.2/8.4 months; mDOR in pts who discontinued due to AE was not reached in M750. Grade 3-4 immune-related adverse events (irAEs) were higher at M750 (46.9% vs 24.2%), although nearly half of events did not require steroids and nearly all non-endocrine irAEs resolved. There was increased T cell proliferation at both doses and greater T cell activation in M750 vs M500. Volrustomig is a novel bispecific antibody with high degree of efficacy in 1L aRCC and across IMDC risk groups, with a low rate of upfront treatment failure. The safety profile is consistent with dual checkpoint inhibition. Volrustomig with lenvatinib is also being evaluated in 1L aRCC (NCT04522323).