ALLO-316 in advanced clear cell renal cell carcinoma (ccRCC): Updated results from the phase 1 TRAVERSE study.

4508 Background: Treatment options are limited for ccRCC after disease progression on immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor (VEGF) inhibitors. CD70 is highly expressed on ccRCC. ALLO-316 is an investigational, healthy donor–derived allogeneic CD70 CAR T-cell product designed to recognize and kill both CD70 positive tumor cells and CD70 positive host T cells that drive allorejection. Initial data from the multicenter, phase 1a/b TRAVERSE study (NCT04696731) showed that ALLO-316 had manageable safety and promising antitumor activity. Updated results are presented. Methods: Patients were aged ≥18 years, had advanced ccRCC, ECOG PS of 0 or 1, and disease progression after ICI and VEGF-targeted therapy. After lymphodepletion (LD) with fludarabine and cyclophosphamide ± ALLO-647 (anti-CD52), patients received a single infusion of ALLO-316 following a 3+3 design (40-240 × 10 6 allogeneic CAR+ T cells). Primary end points were incidence of dose-limiting toxicities and adverse events. Objective response rate (ORR) was a secondary end point. Results: Of 44 patients who underwent LD, 39 received ALLO-316, and 38 were evaluable for disease outcome. Median age was 60 years, median of 3 prior therapies (range, 1-8), and 36 (82%) had CD70 positive ccRCC. As of January 2, 2025, median follow-up was 6.8 months (range, 0.8-39.5). Dose-limiting toxicities occurred in 2 patients (autoimmune hepatitis and cardiogenic shock in the setting of multiorgan failure). Treatment-emergent adverse events occurred in 42 patients (96%; grade ≥3, 37 patients [84%]). Grade ≥3 CRS occurred in 1 patient (2%; any grade, 25 patients [57%]), grade ≥3 ICANS in 0 patients (any grade, 4 patients [9%]), and grade ≥3 IEC-HS in 1 patient (2%; any grade, 8 patients [18%]). No GvHD occurred. As previously reported, 3 grade 5 adverse events were related to ALLO-316 (cardiogenic shock, failure to thrive, and sepsis). ORR for all LD regimens was 20% (6/30) overall for patients with CD70 positive tumors (Table). Confirmed ORR was 33% (3/9) for patients with CD70 ≥50% treated with the phase 1b regimen; all confirmed responses were ongoing (2.1, 6.7, and 8.4 months at the data cut-off). Conclusions: After a median follow-up of 6.8 months, a single infusion of ALLO-316 had manageable safety and encouraging antitumor activity in heavily pretreated patients. Further evaluation of ALLO-316 in CD70 positive ccRCC is warranted. Clinical trial information: NCT04696731 . All CD70 positiven = 30 CD70 positive receiving phase 1b regimen a n = 12 CD70 negative or unknownn = 8 Best overall response (CR or PR at any visit), n/N (%) 8/30 (27) 4/12 (33) 0/8 (0) CD70 ≥50 b 8/24 (33) 4/9 (44) – CD70 <50 b 0/6 (0) 0/3 (0) – ORR (confirmed CR or PR), n/N (%) 6/30 (20) 3/12 (25) 0/8 (0) CD70 ≥50 b 6/24 (25) 3/9 (33) – CD70 <50 b 0/6 (0) 0/3 (0) – a ALLO-316 80 × 10 6 CAR+ T cells and LD with fludarabine 30 mg/m 2 + cyclophosphamide 500 mg/m 2 . b IHC-based tumor proportion score.