Allogene ALLO-316 achieves 31% response rate in solid tumour Phase 1
Allogene Therapeutics has published complete Phase 1 data from the TRAVERSE study of its allogeneic CAR T candidate ALLO-316 in the Journal of Clinical Oncology, reporting a 31% confirmed response rate in patients with advanced renal cell carcinoma (RCC) whose tumours expressed high levels of CD70. The data, generated in collaboration with MD Anderson Cancer Center, represent what the company describes as the first durable remissions achieved with an allogeneic CAR T product in metastatic solid tumours.
The TRAVERSE trial enrolled 51 patients with Stage IV RCC, of whom 46 received ALLO-316 and had a median follow-up of 28.8 months. The Phase 1b expansion cohort, which evaluated the recommended Phase 2 regimen of 80 million CAR T cells following standard fludarabine and cyclophosphamide lymphodepletion, enrolled 22 patients who had failed both immune checkpoint blockade and at least one tyrosine kinase inhibitor; 41% had previously received belzutifan. The median time from enrolment to start of treatment was four days, reflecting the off-the-shelf nature of the product.
Trial results
Among the 20 patients treated with ALLO-316 in Phase 1b, the confirmed overall response rate was 25%. In the 16 patients with a CD70 Tumour Proportion Score of 50% or greater, the confirmed response rate rose to 31%, with all five responders remaining progression-free at the time of the published analysis. Responses ranged from eight to more than 18 months; the median duration of response had not been reached. Median overall survival in the full Phase 1b population was 15.2 months, and was not estimable in the CD70-high subgroup.
The safety profile was consistent with active CAR T therapy. Haematological toxicities dominated: neutropenia and leucopenia occurred in more than 70% of patients at Grade 3 or above, driven largely by the lymphodepletion regimen. Cytokine release syndrome was observed in 68% of patients but produced no Grade 3 or worse events. Immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) occurred in 36%, with two Grade 3 or above cases. There were no Grade 5 events in Phase 1b; three fatal adverse events had occurred in the earlier Phase 1a portion and were previously disclosed. Notably, no cases of graft-versus-host disease were observed across the trial.
Samer Srour of MD Anderson said that for a population who had exhausted available therapies and faced "survival often measured in months", the depth and durability of responses with a one-time infusion were "very promising".
Market and competitive context
The result carries significance beyond RCC. Solid tumours have proven consistently resistant to CAR T approaches that transformed outcomes in haematological cancers such as diffuse large B-cell lymphoma and multiple myeloma. Insufficient CAR T expansion, poor tumour infiltration, and rapid rejection by the host immune system are the primary failure modes. Allogene's Dagger technology addresses immune rejection by engineering ALLO-316 to target CD70 on both tumour cells and CD70-positive alloreactive host T cells, aiming to prolong persistence without intensified lymphodepletion.
Several competitors are pursuing allogeneic CAR T approaches in solid tumours, including Caribou Biosciences and Precision BioSciences, while autologous players such as Iovance Biotherapeutics and Adaptimmune are targeting different solid tumour antigens with engineered cell products. The 31% response rate in a biomarker-selected, heavily pre-treated population, combined with the absence of graft-versus-host disease, gives Allogene a substantive clinical narrative as the field moves toward Phase 2. The FDA's RMAT designation, granted in October 2024, and earlier Fast Track designation position ALLO-316 for potentially expedited review should Phase 2 data replicate the Phase 1b findings. Allogene is expected to outline Phase 2 planning in upcoming investor communications.