Updated results from a phase II study of penpulimab plus anlotinib as first-line therapy in metastatic urothelial cancer (mUC).

4573 Background: Cisplatin-based chemotherapy is the standard-of-care systemic treatment for mUC patients with good physical status and organ function, which has shown a response in more than 40% of patients, with mOS approximately 15 months. With the advent of immune checkpoint inhibitors, there are more explorations and options for first-line treatment of locally advanced or mUC. However, here is an ongoing unmet need for improved first-line treatment. Immune checkpoint inhibitors combined with anti-angiogenic therapy have a synergistic effect. Studies have reported that penpulimab combined with anlotinib have good efficacy and safety in multiple solid tumors. This study aimed to evaluate the efficacy and safety of penpulimab plus anlotinib as first-line therapy for mUC (ChiCTR2200056732). Methods: In the single-arm, phase Ⅱ study, eligible patients were aged 18-75 years with mUC who had no prior systemic therapy and ineligible or rejected for cisplatin-based therapy or any platinum-based chemotherapy, measurable lesion (according to RECIST v1.1), and ECOG PS of 0-2. Patients received penpulimab 200 mg intravenously on day 1 and anlotinib 8 mg orally once daily on day 1 to 14 every 3 weeks until progression, intolerable toxicities, or completion of 24 months of treatment. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: From Feb. 2020 to Dec. 2023, 29 patients of mUC were successfully enrolled and received at least once time treatment. Among them, 79.3% (23/29) were males and 20.7% (6/29) were females, with a median age of 64 years (range, 49-74). 10 of 29 (34.48%) patients had a history of smoking. 24.1% (7/29), 72.4% (21/29) and 3.45% (1/29) patients were ECOG PS 0, 1 and 2, respectively. PD-L1 expression was detected in 25 patients, of whom 52.0% (13/25) had TPS < 1, 36.0% (9/25) had TPS≥1%, <50%, and 12.0% (3/25) had TPS≥50%. At data cutoff (January. 1. 2024), a total of 24 patients were evaluated with a median follow-up time of 8.3m (95% CI, 2.8-13.8). The ORR was 62.5% (95% CI, 40.6-81.2) and DCR was 95.8% (95% CI, 78.9-99.9). The median PFS was 12.1 months (95% CI, 3.5-20.7). The median OS was not reached and 12-month OS rate was 100%. Frequent treatment-related adverse events of all grades included creatinine increased (16.7%) and transaminase elevation (10.0%). Grade 4 toxicity of liver dysfunction occurred in two patient (6.9%). No treatment-related death was observed. Conclusions: Penpulimab plus anlotinib demonstrated promising antitumor activity and manageable safety profile with no new safety signal in mUC. Clinical trial information: ChiCTR2200056732.