Phase 1 radioimmunotherapy study with lutetium 177-labeled anti-carbonic anhydrase ix monoclonal antibody girentuximab in patients with advanced renal cell carcinoma

Background: Patients with metastatic clear cell renal cell carcinoma (ccRCC) have a dismal prognosis. Therefore, new and less toxic treatments are needed. Objective: We determined the maximum tolerated dose (MTD) and potential therapeutic efficacy of multiple infusions of lutetium 177 (¹⁷⁷Lu)- girentuximab (cG250) on various dose levels in a phase 1 trial in patients with progressive metastasized ccRCC. Design, setting, and participants: In this uncontrolled case series in 23 patients with progressive ccRCC metastases, cG250 accumulation was verified by diagnostic indium 111-cG250 imaging. Patients then received a high-activity dose of ¹⁷⁷Lu-cG250. Intervention: Groups of three patients received ¹⁷⁷Lu-cG250, starting at a dose level of 1110 MBq/m^{2 177}Lu-cG250, with dose increments of 370 MBq/m² per group. In the absence of persistent toxicity, progressive disease, and accelerated blood clearance, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. Patients could receive a total of three treatment cycles. Outcome measurements and statistical analysis: Determination of the MTD was the primary and therapeutic efficacy was the secondary outcome measurement of the study. Results and limitations: The MTD was 2405 MBq/m² because higher doses resulted in dose-limiting myelotoxicity. Some patients received second (13 of 23 [56%]) and third (4 of 23 [17%]) treatment cycles. Most patients (17 of 23 [74%]) demonstrated stable disease 3 mo after the first treatment, and one patient showed a partial response that lasted for 9 mo. Mean growth of target tumor lesions was reduced from 40.4% (95% confidence interval [CI], ±17.0) during the last 3 mo before study entry to 5.5% (95% CI, ±5.3; p < 0.001) at 3 mo after the first treatment cycle. No major nonhematologic side effects were observed. Conclusions: ¹⁷⁷Lu-cG250 radioimmunotherapy in metastatic ccRCC patients is well tolerated at an activity dose level as high as 2405 MBq/m ² (MTD). Radioimmunotherapy with ¹⁷⁷Lu-cG250 may stabilize previously progressive metastatic ccRCC.