Allogene Therapeutics (Nasdaq: ALLO) has published complete Phase I data from its TRAVERSE trial in the Journal of Clinical Oncology, reporting what the company claims are the first durable remissions achieved with an allogeneic CAR T therapy in metastatic solid tumors — a milestone that has eluded the CAR T field since the modality transformed hematologic oncology a decade ago.
Solid tumors have been the defining failure of CAR T. Approved autologous products from Bristol Myers Squibb, Gilead's Kite, and Novartis have produced durable remissions in liquid cancers, but none has demonstrated equivalent activity in epithelial malignancies. The barriers — poor CAR T expansion in immunosuppressive tumor microenvironments, host immune rejection of allogeneic cells, and inadequate tumor infiltration — have resisted years of engineering effort.
ALLO-316 targets CD70, a TNF superfamily ligand overexpressed on clear cell renal cell carcinoma cells. Critically, CD70 is also expressed on alloreactive host T cells that would otherwise reject the allogeneic product, meaning the CAR simultaneously kills tumor and eliminates the major immune barrier to its own persistence — the mechanistic logic underlying the company's Dagger platform.
In the TRAVERSE Phase I expansion cohort (Phase Ib), 20 heavily pretreated Stage IV RCC patients received ALLO-316 at 80 million CAR T cells following standard fludarabine/cyclophosphamide lymphodepletion. All had failed immune checkpoint blockade and at least one tyrosine kinase inhibitor; 82% had received two or more TKIs and 41% had prior Merck's Welireg (belzutifan). The confirmed overall response rate was 25% (5/20), rising to 31% in the 16 patients with high CD70 tumor proportion scores (≥50%). Median duration of response had not been reached at a data cut with responses ranging from 8 to over 18 months, and all five responders remained progression-free at the time of analysis. Median overall survival was not estimable in the CD70-high subgroup.
The safety profile was broadly consistent with lymphodepletion and an active CAR T product. Grade ≥3 events were predominantly hematologic. Cytokine release syndrome occurred in 68% of Phase Ib patients but produced no Grade 3 or higher events. IEC-HS, a hemophagocytic-like syndrome associated with CAR T hyperactivation, was observed in 36% at any grade, with two Grade ≥3 cases managed using a protocol-defined algorithm. There were no Grade 5 events in Phase Ib, contrasting with three treatment-related deaths in the earlier Phase Ia dose-escalation cohort.