Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
Allogeneic CD70-Targeted Chimeric Antigen Receptor T-Cell Therapy for Advanced Renal Cell Carcinoma: Results From the Phase I TRAVERSE Trial.
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Srour Samer A, Chahoud Jad, Drakaki Alexandra, Curti Brendan D, Gibney Geoffrey T, Tang Lily, Jiang Yizhou, Charmsaz Sara, Robbins Paul B, McLeroy Jeff, Severyn Christopher J, Le Gall John B, Roberts Zachary J, Tannir Nizar M, Pal Sumanta, Kotecha Ritesh R
Аннотация
PURPOSE: Treatment options for clear cell renal cell carcinoma (ccRCC) refractory to immune checkpoint inhibitors (ICIs) and targeted therapy are needed. ALLO-316 is an allogeneic chimeric antigen receptor (CAR) T-cell product that targets CD70-expressing ccRCC and resists immune rejection by targeting and eliminating patients' CD70+ alloreactive T cells.
METHODS: In the phase Ia/b TRAVERSE trial (ClinicalTrials.gov identifier: NCT04696731), patients with advanced ccRCC resistant to ICIs and vascular endothelial growth factor receptor-targeted therapy received lymphodepletion and ALLO-316 following a modified 3 + 3 design. Phase Ia evaluated ALLO-316 dose and fludarabine/cyclophosphamide (FC)-based lymphodepletion with/without the anti-CD52 antibody, ALLO-647. Additional patients were enrolled in phase Ib to confirm the expansion regimen identified in phase Ia. Primary end points were dose-limiting toxicities (DLTs) and adverse events (AEs).
RESULTS: Fifty-one patients were enrolled (phase Ib, n = 23). Patients received a median of four prior lines of therapy. The median follow-up was 28.8 months. DLTs occurred in two patients who received ALLO-647 (grade 3 autoimmune hepatitis; grade 5 cardiogenic shock). Grade ≥3 cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome occurred in 2.0%, 0%, and 6.0% of patients, respectively. Most grade ≥3 AEs were hematologic (neutropenia 62.0%; white blood cell count decreased 54.0%; anemia 36.0%). In phase Ib, patients received FC and 80 × 106 CAR T cells. The objective response rate was 17.4% overall, 25.0% in phase Ib patients and 31.3% in phase Ib patients with CD70 tumor proportion score ≥50%.
CONCLUSION: 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.
METHODS: In the phase Ia/b TRAVERSE trial (ClinicalTrials.gov identifier: NCT04696731), patients with advanced ccRCC resistant to ICIs and vascular endothelial growth factor receptor-targeted therapy received lymphodepletion and ALLO-316 following a modified 3 + 3 design. Phase Ia evaluated ALLO-316 dose and fludarabine/cyclophosphamide (FC)-based lymphodepletion with/without the anti-CD52 antibody, ALLO-647. Additional patients were enrolled in phase Ib to confirm the expansion regimen identified in phase Ia. Primary end points were dose-limiting toxicities (DLTs) and adverse events (AEs).
RESULTS: Fifty-one patients were enrolled (phase Ib, n = 23). Patients received a median of four prior lines of therapy. The median follow-up was 28.8 months. DLTs occurred in two patients who received ALLO-647 (grade 3 autoimmune hepatitis; grade 5 cardiogenic shock). Grade ≥3 cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome occurred in 2.0%, 0%, and 6.0% of patients, respectively. Most grade ≥3 AEs were hematologic (neutropenia 62.0%; white blood cell count decreased 54.0%; anemia 36.0%). In phase Ib, patients received FC and 80 × 106 CAR T cells. The objective response rate was 17.4% overall, 25.0% in phase Ib patients and 31.3% in phase Ib patients with CD70 tumor proportion score ≥50%.
CONCLUSION: 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.