Efficacy of nivolumab plus ipilimumab in T1aN0M0 renal cell carcinoma (RCC) patients: Results from 3-year follow-up of the phase 2 pilot study.

536 Background: Some patients with primary renal cell carcinoma (RCC) are not candidates for surgery or nephron-sparing interventions due to various factors, such as the presence of a functional single kidney with a central, high-complexity tumor. This study aimed to evaluate whether a combination of nivolumab and ipilimumab could eliminate the primary tumor in patients with T1aN0M0 RCC. Methods: This prospective, multicenter, phase 2 pilot study enrolled patients with biopsy-confirmed clear-cell RCC (cT1a) ≤4 cm, no metastases, and who were ineligible for surgery or nephron-sparing procedures. Patients were treated with ipilimumab (1 mg/kg) every 3 weeks for four doses, alongside nivolumab (240 mg) every 2 weeks for eight doses. The primary endpoint was the complete response rate. Simon's two-stage design was used, testing the null hypothesis of a true complete response rate of 11%. A type I error rate of 0.05 and a power of 0.9 were set, with the null hypothesis rejected if 3 or more responses were observed in 8 patients. Results: From February 2020 to June 2021, 8 patients were enrolled, with a median age of 77.9 years (range 73–89). The cohort was entirely Caucasian, predominantly male (75%), and 62.5% had centrally located tumors. Six patients had moderate to severe comorbidities. All patients completed the immunotherapy without experiencing grade ≥2 adverse events. After a median follow-up of 37.4 months (95% CI 31.7–44.5), no complete responses were observed. However, partial responses were seen in 4 patients (50%), with continued tumor reduction after therapy. The median tumor size decreased from 3.11 cm (range 2.2–3.9) to 1.89 cm (range 1.1–4.0). Tumor shrinkage was observed in 6 patients (75%), while 1 patient experienced a slight tumor enlargement (+0.5 cm, +13%) after 9 months. The 3-year progression-free survival rate was 100%. Data on 5-year overall survival will be reported later. Conclusions: Although complete tumor regression was not achieved, immunotherapy with nivolumab and ipilimumab led to significant and durable tumor shrinkage in two-thirds of T1aN0M0 RCC patients, with minimal toxicity, making it a viable option for patients with significant comorbidities. Further data on long-term survival are awaited. Clinical trial information: NCT04134182 .