Multicenter phase 1 trial of allogeneic CD70-targeted CAR T-cell therapy for advanced renal cell carcinoma

There is a need for treatment options for clear cell cell carcinoma (ccRCC) refractory to immune checkpoint inhibitors (ICIs) and targeted therapy. ALLO-316 is an allogeneic CAR T-cell product that targets CD70-expressing ccRCC and resists immune rejection by targeting and eliminating CD70⁺ alloreactive T cells. The multicenter phase 1 TRAVERSE trial in the USA evaluated ALLO-316 in patients with advanced ccRCC resistant to ICIs and VEGFR-targeted therapy. Phase 1a evaluated ALLO-316 dose and fludarabine/cyclophosphamide (FC)-based lymphodepletion with or without the anti-CD52 antibody ALLO-647. Additional patients were enrolled in phase 1b to confirm the expansion regimen identified in phase 1a. Fifty-one patients were enrolled (phase 1b n=23) with a median of four prior lines of therapy. The median follow-up was 28.8 months. Dose-limiting toxicity occurred in two patients who received ALLO-647 (grade 3 autoimmune hepatatis, grade 5 cardiogenic shock. Grade ≥3 CRS, ICANS, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome occurred in 2.0%, 0%, and 6.0% of patients, respectively. The objective response rate was 17.4% overall, 25.0% in phase 1b patients, and 31.3% in phase 1b patients with CD70 tumor proportion score ≥ 50%. The authors conclude that ALLO-316 had manageable safety and encouraging antitumor activity in CD70-positive ccRCC. The TRAVERSE trial demonstrates proof of concept for the role of allogeneic CAR T-cell therapy in solid tumors.