Allogeneic CD70 CAR T-Cell Therapy Shows Activity in Refractory Kidney Cancer

Investigational off-the-shelf chimeric antigen receptor (CAR) T-cell therapy ALLO-316 produced durable responses in heavily pretreated patients with advanced clear cell renal cell carcinoma (ccRCC), according to phase 1a/b (NCT0469673) results from the TRAVERSE trial published in the Journal of Clinical Oncology.¹

In the phase 1b expansion cohort, the objective response rate (ORR) was 25.0% overall and 31.3% among patients whose tumors expressed high levels of CD70, a tumor necrosis factor family molecule expressed on roughly 80% of renal cell carcinomas and most highly in ccRCC.¹ No responses occurred in patients with low or absent CD70 expression, reinforcing biomarker-based patient selection for this therapy. Median overall survival in the phase 1b population was 15.2 months and was not estimable in the CD70-high subgroup.

ALLO-316 is a human leukocyte antigen–unmatched, allogeneic CAR T-cell product manufactured from healthy donor T cells using TALEN-based gene editing to eliminate the T-cell receptor and knock out CD52, a design intended to prevent graft-vs-host disease (GVHD) while permitting concurrent use of the anti-CD52 antibody ALLO-647 during lymphodepletion.

“There are additional edits, like masking the CD70 expression. It also knocks out the direct gene which prevents [GVHD]. In addition to that, this novel agent has a safety switch. If the patient had excessive, unexpected toxicity, we could use a CD20 antibody to kill it,” said Samer Srour, MB, ChB, MS, assistant professor, department of Stem Cell Transplantation, Division of Cancer Medicine, UT MD Anderson, and investigator of the TRAVERSE trial, in a previous interview with Targeted Oncology^TM.

Study Background

The multicenter, open-label study enrolled 51 patients with advanced ccRCC that had progressed on immune checkpoint inhibitors and vascular endothelial growth factor receptor–targeted therapy, a population with a median of 4 prior lines of treatment.² Phase 1a used a modified 3+3 dose-escalation design to test four ALLO-316 dose levels combined with fludarabine/cyclophosphamide (FC) lymphodepletion, with or without ALLO-647 (FCA). Two dose-limiting toxicities occurred in the FCA cohort—grade 3 autoimmune hepatitis and a fatal case of cardiogenic shock associated with hyperinflammation—prompting a halt to FCA enrollment and a safety review. Enrollment resumed with FC lymphodepletion alone at a lower CAR T-cell dose of 80 × 10⁶ cells, the regimen ultimately selected for phase 1b.¹

Safety and Tolerability

Across the full cohort of 50 patients evaluable for safety, treatment-emergent adverse events of grade 3 or higher occurred in 92%, predominantly hematologic (neutropenia, 62%; white blood cell count decreased, 54%; anemia, 36%). Grade 3 or higher cytokine release syndrome occurred in 2% of patients, with no grade 3 or higher immune effector cell–associated neurotoxicity syndrome reported—rates the authors note compare favorably with published data for autologous CD19-directed CAR T-cell products in hematologic malignancies.

Immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), a toxicity of particular concern in this program, occurred in 24% of patients overall (grade 3 or higher, 6%). A mid-trial protocol amendment introducing standardized diagnostic and grading criteria, along with treatment incorporating the Janus kinase inhibitor ruxolitinib (Jakafi), was associated with improved control of IEC-HS in later-enrolled patients, with no grade 5 events among the final 20 patients treated.

Pharmacokinetic analyses showed that CAR T-cell expansion, measured by vector copy number, was greater with FC than FCA lymphodepletion, and responders demonstrated higher peak expansion and 28-day area under the curve than nonresponders.

The authors acknowledge several limitations to the study design, including a small sample size, short follow-up, absence of a control arm, lack of a standardized CD70 positivity threshold, and a study population that was predominantly male and White.

REFERENCES

1. Srour SA, Chahoud J, Drakaki A, et al. Allogeneic CD70-Targeted Chimeric Antigen Receptor T-Cell Therapy for Advanced Renal Cell Carcinoma: Results From the Phase I TRAVERSE Trial. J Clin Oncol. 0, JCO-26-00388. doi::10.1200/JCO-26-00388

2. Safety and Efficacy of ALLO-316 in Subjects With Advanced or Metastatic Clear Cell Renal Cell Carcinoma (TRAVERSE). ClinicalTrials.gov. Updated July 17, 2026. Accessed July 21, 2026. https://clinicaltrials.gov/study/NCT04696731