3D render of human kidney on science background: © Rasi – stock.adobe.com
The updated results from the phase 1 TRAVERSE study (NCT04696731) of ALLO-316 in advanced clear cell renal cell carcinoma (ccRCC) demonstrate a confirmed objective response rate of 25%, rising to 31% in patients with high CD70 expression, with some ongoing durable responses exceeding 1 year.1
ALLO-316, an off-the-shelf allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD70, showed a manageable safety profile and an encouraging antitumor activity. Notably, the product achieved robust CAR T-cell persistence beyond 3 months in some patients, a rare feature in allogeneic CAR T therapies. These results support further development of ALLO-316 in RCC and other solid tumors, and paves the way for a phase 2 study in the near future.
In an interview with Targeted OncologyTM, Samer A. Srour, MD, associate professor, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, discussed with Targeted OncologyTM updated data from the TRAVERSE study presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
Targeted OncologyTM: What is the background and rationale behind the TRAVERSE study?
Srour: The TRAVERSE study is the first-in-human phase 1 clinical trial exploring ALLO-316, a CD70-targeted allogeneic CAR T-cell product for patients with advanced or metastatic renal cell carcinoma who failed checkpoint inhibitors and tyrosine kinase inhibitors. We presented in the past our phase 1a dose escalation data at several meetings with encouraging early results. After exploring 4 different dose levels and 4 different lymphodepletion (LD) platforms, we established our phase 1 expansion dose at a flat dose of 80 million ALLO-316 cells and using standard LD chemotherapy consisting of fludarabine and cyclophosphamide. For this presentation, we presented updated phase 1b data showing manageable safety and encouraging efficacy results.
What is the patient inclusion criteria and what was being evaluated?
For the phase 1b data, our primary endpoint was safety, and the secondary endpoint was efficacy, including confirmed objective response rate, durability of response, survival, and also the cell kinetics. Patients should have advanced or metastatic clear cell renal cell carcinoma and failed at least a checkpoint inhibitor and a tyrosine kinase inhibitor to be eligible for the study. Patients should otherwise be fit and meet eligibility which are common to any other CAR T-cell therapy study. Patients with treated brain metastasis were allowed.
What were the key updated findings that were presented at ASCO?
In this phase 1b cohort of this study, we enrolled 22 heavily pretreated patients, of which 20 patients were infused with ALLO-316. The median age was 56 (range, 35-67) years. Median prior lines of therapy was 4, 59% received 3 or more TKIs and 32% of the patients had received 4 different classes of kidney cancer drugs prior to enrollment. That tells indeed how heavily pretreated these patients are, have limited treatment options and with an overall dismal prognosis. Because ALLO-316 is an allogeneic off-the-shelf product, we were able to treat patients very quickly once deemed candidates for the study, with a median time from enrollment to treatment of only 4 days. We had patients treated almost 1 day after enrollment. This is a great achievement compared to the commercially available autologous CAR T-cell products that are approved in several hematological malignancies.
Regarding outcome data, overall, I would say the safety profile was manageable and was consistent with what we see in other CAR T-cell products such as cytokine release syndrome, cytopenias and infections. For instance, cytokine release syndrome, 68% of our patients had grade 1 or 2 cytokine syndrome. Four patients (18%) had ICANS, all were low-grade and transient. No cases of graft-vs-host disease were reported. One notable toxicity to talk about, which is increasingly more recognized in recent years, is an HLH-like syndrome, which happens in the context of CAR T-cell or immunotherapy. We call it IEC-HS (immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome). Thirty-six percent of our patients did develop this toxicity, which is a somewhat higher than expected when compared to commercially available CAR T-cell therapies, but something we are seeing more frequently in other clinical trials in the solid tumors space. We learned much over the course of the phase 1a data about this once-considered very serious complication, and then we adapted into our phase 1b an algorithm on how to capture this toxicity at the earliest signs and intervene promptly without using excessive immunosuppression. Most of the IEC-HS cases were captured early at grades 1-2 and managed based on our algorithm. And to that point, we didn’t encounter in the phase 1b cohort any dose-limiting toxicities related to HLH. I think the algorithm we followed was a successful strategy to manage HLH without compromising the efficacy of the product, and hence may have contributed to our positive promising results.
Talking about the efficacy data, again, it is important to mention these are heavily treated patients who have limited options, and many patients failed all standard therapies known to confer clinical benefit with some having no options except for best supportive care alone vs. the clinical trial. In this patient population, our confirmed objective response rate (ORR)—meaning patients who have partial response or complete remission—was 25% for all patients, but if we look at the patients who have high CD70 expression, the confirmed ORR was 31%. What is more interesting and encouraging, most of these responses were actually durable with only 1 of the 5 objective responses having progressed at the last time of follow-up.
In addition to safety and efficacy data, it is important to mention the unique translational and correlative outcomes data we found in the TRAVERSE study. I do run several other clinical trials, including other off-the-shelf allogeneic products, and it has always been a challenge for us to improve on the persistence of the cells in these allogeneic products—especially beyond 4-5 weeks after the infusion, something we were able to see with ALLO-316. One of the unique features of ALLO-316 is its ability to deplete the host CD70+ T cells, which may have allowed for better engraftment for the CAR T-cell product and robust expansion and persistence over time. It is very important to highlight this unique feature of ALLO-316. We call this the “Dagger effect,” where the CAR T-cell product itself is able to deplete the host CD70+ T cells, and then refuel its own persistence over time, which may have contributed to the encouraging responses.
Looking at ALLO-316, what are the potential advantages that it may offer over autologous or traditional T cell therapies?
One of the biggest barriers to adopting and implementing autologous CAR T-cell therapy is the time it takes to manufacture these cells. From the screening to enrolling patients, to collecting the cells, manufacturing, and treating, it takes at minimum 5 to 6 weeks, and it takes longer in real practice, when these products are approved. For the off-the-shelf products, these CAR T cells are already manufactured from donated cells from healthy donors, and hence the cells are ready for infusion once patients are identified. As I mentioned earlier, the median time from enrollment to treatment was only 4 days which is a great advantage over autologous products. Indeed, in our experience with this study, many patients presented to us having rapidly progressive disease, to the point that even waiting a few days, or even during the lymphodepletion and before infusion, patients deteriorated so fast that they couldn’t get the treatment.
So, having an off-the-shelf readily available product for our patients, with very rapid turnaround in a few days, can be lifesaving to many patients who otherwise cannot wait a few weeks for an autologous CAR T-cell therapy.
What are the next steps for this research, or for ALLO-316 as a whole?
First, I would like to mention that it is always encouraging to see any allogeneic or autologous CAR T-cell product working in solid tumors. It just gives us hope that we were able to make a breakthrough achievement in the solid tumor space. Because, as you know, all the FDA-approved CAR T-cell products are for hematological malignancies.
It is exciting that in the past year we have had two cell therapy products—tumor-infiltrating lymphocyte and T-cell receptors—approved for small patient populations in melanoma and sarcoma, but we have yet to see it for a CAR T-cell product. So, having such an encouraging objective response rate with ALLO-316 in heavily treated advanced/metastatic RCC patients in our phase 1b cohort—and the fact that many of these responses are ongoing—it just gives us hope that we may be getting close to some breakthrough CAR T-cell approval in the solid tumor space.
The TRAVERSE study reaffirms the promise for moving the field forward in RCC and other solid tumors, In summary, it is a proof of concept that we are able to make a breakthrough achievement with CAR T-cell therapy in solid tumors. Particularly for the TRAVERSE study, we are looking forward to build on these encouraging phase 1b data for a possible registrational phase 2 study in the near future, and to expand into other CD70 positive tumors.