A phase Ib/IIa trial to evaluate the safety and efficacy of PM8002/ BNT327, a bispecific antibody targeting PD-L1 and VEGF-A, as a monotherapy in patients with advanced renal cell carcinoma

BackgroundLimited therapeutic options are available for patients (pts) with second-line advanced clear cell renal cell carcinoma (ccRCC) and previously untreated non-clear cell renal cell carcinoma (nccRCC). PM8002 is a bispecific antibody targeting both PD-L1 and VEGF-A. Here, we report the results from an ongoing Phase Ib/IIa trial of ccRCC and nccRCC pts treated with PM8002.MethodsPatients with second line ccRCC with prior 1L IO and VEGF targeted therapy combination or 1L VEGF targeted therapy monotherapy and untreated nccRCC pts were enrolled in a phase I/IIa trial. All pts received PM8002 as a single agent until observations of unacceptable toxicity, disease progression or consent withdrawal. Tumor responses were evaluated every 6 weeks during the first year, followed by every 12 weeks. The primary endpoint was objective response rate (ORR).ResultsAs of March 15, 2024, 53 pts had received at least one dose of PM8002, of which 50 pts had completed at least one tumor evaluation, including 28 pts with ccRCC and 22 pts with nccRCC. 28 pts with ccRCC had received prior 1L treatment, 21.4% pts of which had IO treatment. The histology of the 22 pts with nccRCC included papillary (n=10,45.5%), FH-deficient RCC(n=3,13.6%), TFE3-rearranged RCC (n=4,18.2%), translocation RCC (n=1, 4.5%), ESC RCC (n=2, 9.1%), oncocytoma (n=1, 4.5%) and chromophobe (n=1, 4.5%). Promising efficacy was observed both in ccRCC and in nccRCC (table). In two cohorts, all pts experienced treatment-related adverse events (TRAE), with ≥ Grade 3 TRAEs of 39.6% (21/53). Any-grade immune-related adverse events (irAE) occurred in 49.1% (26/53) of pts with ≥ Grade 3 irAEs of 3.8% (2/53). Serious adverse events (SAE) and treatment-related SAEs were observed in 15.1% (8/53) and 7.5% (4/53) of pts, respectively. Table: 1692P Summary of efficacy results PM8002/BNT-327 monotherapy ccRCC N=28 nccRCC N=22 ORR, n (%) (95% CI) 25.0 (10.7, 44.9) 36.4 (17.2,59.3) DCR, n (%) (95% CI) 78.6 (59.1, 91.7) 90.9 (70.8,98.9) mPFS, m (95% CI) 10.9 (5.7, -) 15.1 (5.1, -) 6m PFS rate, (95% CI) 65.4 (43.8,80.3) 74.4 (48.6,88.6) ConclusionsPM8002 showed encouraging antitumor activity and acceptable safety in pts with advanced second-line ccRCC and untreated nccRCC.Clinical trial identificationNCT05918445.Legal entity responsible for the studyBiotheus Inc.FundingBiotheus Inc.DisclosureAll authors have declared no conflicts of interest.