Treatment options remain limited for patients with advanced clear cell renal cell carcinoma who experience disease progression after immune checkpoint inhibitors and vascular endothelial growth factor receptor–targeted therapy.
Results from the phase Ia/b TRAVERSE trial provide early evidence that ALLO-316, an off-the-shelf allogeneic chimeric antigen receptor T-cell therapy targeting CD70, can produce antitumor responses in heavily pretreated patients, particularly among those with high tumor CD70 expression.
The article, titled “Allogeneic CD70-Targeted Chimeric Antigen Receptor T-Cell Therapy for Advanced Renal Cell Carcinoma: Results From the Phase I TRAVERSE Trial,” was published in the Journal of Clinical Oncology on July 14, 2026.
Authors: Samer A. Srour, Jad Chahoud, Alexandra Drakaki, Brendan D. Curti, Geoffrey T. Gibney, Lily Tang, Yizhou Jiang, Sara Charmsaz, Paul B. Robbins, Jeff McLeroy, Christopher J. Severyn, John B. Le Gall, Zachary J. Roberts, Nizar M. Tannir, Sumanta Pal, and Ritesh R. Kotecha.
Why Target CD70?
CD70 is an immunoregulatory molecule that is abnormally expressed in several cancers. Approximately 80% of renal cell carcinomas express CD70, with the highest expression observed in clear cell renal cell carcinoma.
Other than immune cells, CD70 has limited expression in normal tissues, making it an attractive target for CAR T-cell therapy.
ALLO-316 is an HLA-unmatched, healthy donor–derived CAR T-cell product designed to recognize CD70-expressing tumor cells. It was also engineered to eliminate CD70-positive alloreactive T cells that could otherwise reject the donor-derived product and limit CAR T-cell expansion and persistence.
The product incorporates gene-editing modifications intended to prevent graft-versus-host disease and enable the use of an anti-CD52 antibody during lymphodepletion.
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TRAVERSE Trial Design
TRAVERSE, or NCT04696731, was a first-in-human, open-label, multicenter phase Ia/b trial involving adults with advanced or metastatic clear cell renal cell carcinoma.
Eligible patients had measurable disease according to RECIST v1.1, an ECOG performance status of 0 or 1, and previous treatment with both an immune checkpoint inhibitor and VEGFR-targeted therapy. Patients had experienced disease progression or discontinued treatment because of toxicity.
The study initially enrolled patients without requiring CD70 expression. After the first 19 patients, the protocol was amended to require a CD70 tumor proportion score of at least 1%.
Phase Ia evaluated different ALLO-316 doses and lymphodepletion regimens. Patients received fludarabine and cyclophosphamide, with or without the anti-CD52 antibody ALLO-647, followed by a single intravenous infusion of ALLO-316.
The primary endpoints were dose-limiting toxicities and adverse events. Secondary endpoints included objective response rate, duration of response, overall survival, CAR T-cell expansion, and immunogenicity.
Patient Population
Between March 15, 2021, and February 13, 2025, 51 patients were enrolled across 10 centers.
The safety population included 50 patients who received lymphodepletion, while 46 patients received ALLO-316 and were included in the efficacy analysis. Patients had received a median of four previous lines of therapy, and the median follow-up was 28.8 months.
Among the safety population, 84% had CD70-positive tumors and 66% had CD70-high tumors, defined as a tumor proportion score of at least 50%. The median age was 60 years, and 88% of patients were male.
Phase Ib Regimen
During phase Ia, two dose-limiting toxicities occurred in patients who received lymphodepletion containing ALLO-647: grade 3 autoimmune hepatitis and grade 5 cardiogenic shock.
Following safety reviews and protocol modifications, the phase Ib regimen consisted of fludarabine at 30 mg/m² per day and cyclophosphamide at 500 mg/m² per day for three days, followed by a single infusion of 80 × 10⁶ ALLO-316 CAR T cells.
Phase Ib included 23 patients: six patients from phase Ia who received the selected expansion regimen and 17 additional patients. Twenty-two received lymphodepletion and were evaluable for safety, while 20 received ALLO-316.
Antitumor Activity
Across all 46 patients treated with ALLO-316, eight confirmed partial responses were reported, corresponding to an objective response rate of 17.4%. The disease control rate was 58.7%.
Activity was higher in phase Ib, where five of 20 patients achieved a confirmed partial response, resulting in an objective response rate of 25%.
Among 16 phase Ib patients with CD70-high tumors, five responded, corresponding to an objective response rate of 31.3%. No responses occurred among the four patients whose CD70 tumor proportion score was below 50%.
Seven of the 20 phase Ib patients experienced a reduction of more than 30% in target-lesion size. Responses were observed regardless of previous therapy and generally occurred within 28 days of ALLO-316 infusion.
The median duration of response was not estimable. No disease progression events occurred among responders after a minimum follow-up of eight months.
Median overall survival was 15.2 months in the overall phase Ib population and was not estimable in the CD70-high subgroup. Patients whose best response was stable disease maintained disease control for a median of 3.75 months.
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Safety Findings
Treatment-emergent adverse events occurred in all 50 patients in the safety population, with grade 3–5 events reported in 92%.
The most common grade 3 or higher adverse events were hematologic, including neutropenia in 62%, decreased white blood cell count in 54%, and anemia in 36%.
Across the overall population, grade 3 or higher cytokine release syndrome occurred in 2% of patients. No grade 3 or higher immune effector cell–associated neurotoxicity syndrome was reported, while grade 3 or higher immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome, or IEC-HS, occurred in 6%.
Three fatal treatment-related adverse events occurred during phase Ia: cardiogenic shock, failure to thrive, and sepsis. Enrollment was temporarily paused while investigators reviewed the emerging safety findings and developed more detailed diagnostic criteria and a grade-based treatment algorithm for IEC-HS.
In phase Ib, grade 1 or 2 cytokine release syndrome occurred in 68.2% of patients, with no grade 3 or higher events. Infections occurred in 50%, including grade 3 or higher infections in 40.9%. IEC-HS occurred in 36.4%, including grade 3 or higher events in 9.1%, while ICANS occurred in 18.2%, with no grade 3 or higher events. No grade 5 treatment-related adverse events or graft-versus-host disease occurred in phase Ib.
CAR T-Cell Expansion and Tumor Infiltration
Paired blood and tumor samples demonstrated that ALLO-316 cells could infiltrate tumor tissue in both responders and nonresponders. Responders had greater CAR T-cell expansion during the first 28 days than nonresponders. There was also a trend toward greater CAR T-cell expansion in patients with CD70-high tumors compared with those with lower CD70 expression.
CAR T-cell levels gradually decreased and were close to the lower limit of detection by day 240. These findings supported the proposed mechanism of ALLO-316, which was designed to target both CD70-expressing cancer cells and CD70-positive alloreactive T cells that could contribute to rejection of the donor-derived product.
Study Limitations
The main limitations included the small patient population, relatively short follow-up, absence of a control arm, investigator-assessed responses, and the lack of a rigorously defined CD70 cutoff. The protocol also underwent several amendments during the early stages of the study. In addition, the population was predominantly male and White, which may limit the generalizability of the findings. Although higher CD70 expression was associated with greater activity, the optimal biomarker threshold requires validation in larger studies.
Conclusion
The phase I TRAVERSE trial showed that a single infusion of ALLO-316 could produce responses in heavily pretreated patients with advanced clear cell renal cell carcinoma, with the strongest activity observed in patients whose tumors had high CD70 expression.
Three fatal treatment-related adverse events occurred during phase Ia, prompting safety reviews, protocol changes, and tailored monitoring and treatment strategies. No grade 5 treatment-related adverse events were subsequently reported in phase Ib.
The findings provide proof-of-concept evidence supporting further evaluation of allogeneic CD70-targeted CAR T-cell therapy in clear cell renal cell carcinoma and other CD70-positive tumors.
The full article is available in the Journal of Clinical Oncology.
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