Interim analysis results from a phase II study of adjuvant penpulimab in very high-risk clear cell renal cell carcinoma

BackgroundThe keynote-564 study showed that adjuvant pembrolizumab improved disease-free survival (DFS) in high-risk clear cell renal cell carcinoma (ccRCC) patients. However, subgroup analysis showed that not all patients benefited. Hence, we aim to explore the efficacy and safety of penpulimab after nephrectomy in ccRCC with a very high-risk of recurrence.MethodsIn this prospective, standard of care-controlled, phase Ⅱ trial, eligible ccRCC patients were aged 18-80 years with a very high-risk (pT3aG1-G2 and ≥2 pT3a factors, pT3aG3-G4, pT3b or higher, regional lymph-node metastasis, or stage M1 with NED) of recurrence who after surgery, without prior targeted therapy or immunotherapy, and ECOG PS of 0 or 1. Patients received penpulimab 200 mg intravenously on day 1 every 3 weeks until progression, intolerable toxicities, or completion of 17 cycles, or observation after surgery. Primary endpoint was DFS. Secondary endpoints included overall survival and safety.ResultsBetween July 2022 and March 2024, 63 patients were enrolled to receive penpulimab (n=31) or observation (n=32). Most patients in the penpulimab group had M1 NED status (19.4%) than the control group (3.1%). The group of individuals who were treated with penpulimab had a higher risk than the control group (P=0.040). At data cutoff of April 25, 2024, median follow-up for the penpulimab and control groups were 8.3m (95% CI: 5.1-11.5) and 5.7m (95% CI: 2.8-8.6), respectively. During follow-up, 2 and 5 patients had recurrence respectively. mDFS was not reached in the penpulimab group, and 11.2m in the control group (HR 0.21, 95% CI 0.04-1.16). The 7-month DFS rate in the penpulimab and control group were 89.3% and 82.1%, respectively. There was a beneficial trend in the penpulimab group. In the penpulimab group, the TRAE was 93.6% (29/31), mainly Grade 1-2, without Grade 3 and only 1 case of Grade 4, which was immune-related myositis. Most common TRAEs were proteinuria (35.48%), rash (32.26%), alanine aminotransferase increased (19.35%). No treatment-related death was observed.ConclusionsAdjuvant penpulimab demonstrated promising antitumor activity and manageable safety profile in ccRCC with a very high-risk of recurrence.Clinical trial identificationChiCTR2200062189.Legal entity responsible for the studyChinese PLA General Hospital.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.