Top Takeaways From the Phase 2 Trial
- Adjuvant penpulimab significantly improved disease-free survival vs surveillance in patients with very high-risk clear cell renal cell carcinoma, with 1-year DFS rates of 94.3% vs 80.5% and 2-year DFS rates of 88.7% vs 75.4%, respectively; overall survival data remain immature.
- The DFS benefit was generally consistent across prespecified subgroups, including older patients, those with ECOG performance status of 0, those with M0 disease, those with very high-risk T3 disease, and those who underwent radical nephrectomy.
- Penpulimab demonstrated a manageable safety profile, with most treatment-related adverse effects (TRAEs) being grade 1 or 2, a 6.9% rate of grade 3/4 TRAEs, and no treatment-related deaths.
How was the phase 2 trial designed?
The multicenter, open-label, nonrandomized, controlled trial enrolled patients aged 18 to 80 years with histologically confirmed ccRCC and very high-risk features for postoperative recurrence.1 Patients were also required to have an ECOG performance status of 0 or 1, have adequate organ function, and not have received prior systemic antitumor therapy.
Eligible patients were enrolled after nephrectomy. Patients in the adjuvant treatment group received intravenous penpulimab at 200 mg every 3 weeks for up to 17 cycles. Those in the observation group underwent protocol-defined postoperative surveillance alone, without adjuvant systemic therapy.
The primary end point was DFS. Secondary end points included OS and safety.
At baseline, the median age in the overall population (n = 174) was 61.0 years (IQR, 55.0-67.0). Most patients were younger than 65 years (67.82%), were male (72.99%), had an ECOG performance status of 0 (89.08%), had undergone a radical nephrectomy (89.66%), had primary tumor stage T3a disease (74.14%), had N0 disease (93.68%), had M0 disease (95.40%), or did not have sarcomatoid features (88.51%).
What additional data were shared in the publication?
Findings from prespecified subgroup analyses revealed that the association between penpulimab and improved DFS was generally consistent. Favorable trends were observed among patients 65 years and older (HR, 0.32; 95% CI, 0.12-0.89; P = .030), those with ECOG performance status 0 (HR, 0.38; 95% CI, 0.16-0.91; P = .029), those with M0 disease (HR, 0.33; 95% CI, 0.13-0.84; P = .020), those with very-high risk T3 disease (HR, 0.36; 95% CI, 0.13-0.84; P = .048), and those who underwent radical nephrectomy (HR, 0.36; 95% CI, 0.14-0.92; P = .032).
In terms of safety, 49.4% of patients who received penpulimab experienced at least 1 treatment-related adverse effect (TRAE); most TRAEs were grade 1 or 2. Grade 3 or 4 TRAEs were reported at a rate of 6.9%. The most common any-grade TRAEs included rash (24.1%), proteinuria (17.2%), pruritus (12.6%), hypothyroidism (11.5%), fatigue (9.2%), and hyperthyroidism (8.0%). Serious TRAEs occurred in 5.7% of patients, and no treatment-related deaths were observed.
“Patients who progressed exhibited consistent suppression of antitumor immune-related plasma proteins, along with depletion of gut microbiota-associated immunostimulatory metabolites and enrichment of metabolites indicative of metabolic reprogramming, both at baseline and after treatment,” Wang and coauthors wrote. “Importantly, integrated plasma multiomic analyses further identified a set of candidate plasma biomarkers strongly associated with disease progression within the adjuvant treatment cohort.”
References
- Wang Y, Wang D, Zhao H, et al. Adjuvant penpulimab in very-high risk clear cell renal cell carcinoma: a prospective, non-randomized, controlled phase II trial with integrated plasma multi-omics analyses. J Immunother Cancer. 2026;14(7):e015686. doi:10.1136/jitc-2026-015686
- FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma. FDA. Updated April 24, 2025. Accessed July 13, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-penpulimab-kcqx-non-keratinizing-nasopharyngeal-carcinoma
