ALLO-316 for Kidney Cancer

(TRAVERSE Trial)

Not currently recruiting at 10 trial locations

Overseen By Allogene

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Allogene Therapeutics

Must not be taking: Anti-CD70, Anti-CD52

Disqualifiers: CNS metastasis, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Dose escalation phase

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment called ALLO-316, a type of CAR T-cell therapy, for individuals with advanced kidney cancer, specifically clear cell renal cell carcinoma. Researchers seek to determine the optimal dose for future studies. Participants should have previously tried certain cancer treatments, such as checkpoint inhibitors and VEGF inhibitors, and must have a clear cell kidney cancer diagnosis. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions a lymphodepletion regimen, which might require changes to your medication. It's best to discuss this with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ALLO-316 appears safe for patients with advanced kidney cancer. In earlier studies, patients who received a single dose of ALLO-316 managed well, even after trying many other treatments. Reports indicated that patients tolerated the treatment without severe side effects that would prevent continuation.

This treatment is part of a Phase 1 trial, the first step in testing a new treatment in people. These trials focus on determining treatment safety. Although this stage doesn't provide all the answers, initial results for ALLO-316 are promising.

In summary, patients have responded well to ALLO-316 so far. It targets specific cancer cells, potentially reducing unwanted side effects. However, more research is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ALLO-316 for kidney cancer because it offers a novel approach compared to current treatments like targeted therapies and immunotherapy. ALLO-316 is an allogeneic CAR T-cell therapy, which means it uses genetically engineered immune cells from healthy donors to target cancer cells. This is different from existing treatments that often rely on the patient's own immune system, which may be compromised. The potential of ALLO-316 to provide a more robust and immediate immune response against cancer cells is what makes it stand out.

What evidence suggests that ALLO-316 might be an effective treatment for kidney cancer?

Research has shown that ALLO-316, which participants in this trial may receive, offers promising results for treating advanced or metastatic clear cell renal cell carcinoma, a type of kidney cancer. In studies, a single dose led to a 31% confirmed overall response rate (ORR), meaning nearly one-third of patients experienced tumor shrinkage or disappearance. The treatment demonstrated targeted activity against tumors, particularly in patients who had previously tried many other therapies without success. After about seven months of follow-up, the treatment exhibited manageable safety and encouraging outcomes. ALLO-316 targets CD70, a protein found on cancer cells, providing a new approach to tackling this challenging cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer (clear cell renal cell carcinoma) who have already tried certain other cancer treatments. Participants need to be relatively healthy and active, without serious brain metastases or CNS issues, no recent anti-CD70 or anti-CD52 therapies, and no other cancers in the last 3 years.

Inclusion Criteria

My kidney cancer is mainly made up of clear cells.

You have at least one specific type of tumor that can be measured according to certain guidelines.

I have been treated with drugs targeting the immune system and blood vessel growth for my advanced cancer.

Exclusion Criteria

I have not received anti-CD52 monoclonal antibody treatment in the last year.

I have a significant brain or nerve condition affecting my daily life.

Patients unwilling to participate in the extended safety monitoring period

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647

1-2 weeks

Treatment

Participants receive ALLO-316 following the lymphodepletion regimen

Dose escalation phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALLO-316
• Cyclophosphamide
• Fludarabine

Trial Overview The TRAVERSE study is testing ALLO-316's safety and effectiveness after a treatment that reduces immune cells (lymphodepletion) using Fludarabine, Cyclophosphamide, and ALLO-647. It's an early-phase trial to find the right dose for Phase 2.

How Is the Trial Designed?

Group I: ALLO-647, ALLO-316 Experimental Treatment 4 Interventions

ALLO-316 is already approved in United States for the following indications:

Approved in United States as ALLO-316 for:

• Advanced or metastatic clear cell renal cell carcinoma

Who Is Running the Clinical Trial?

Allogene Therapeutics

Lead Sponsor

Trials

7

Recruited

810+

Headquarters

South San Francisco, USA

Known For

Allogenic CAR T

Top Products

Cemacabtagene ansegedleucel (cema-cel), ALLO-501, ALLO-501A, ALLO-316

Published Research Related to This Trial

In a study of 124 patients with metastatic renal cell carcinoma (RCC) undergoing allogeneic hematopoietic stem cell transplantation (HSCT), the treatment showed promising results with a 2-year survival rate of 70% for patients who developed chronic graft-versus-host disease (GVHD) and received donor lymphocyte infusions (DLI).

The study found that factors such as having fewer than three metastatic sites, a Karnofsky score greater than 70%, and the presence of chronic GVHD significantly improved survival rates, indicating that HSCT can be a viable option for select patients with RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe. Barkholt, L., Bregni, M., Remberger, M., et al.[2021]

All patients with renal cell carcinoma (RCC) expressed at least one tumor-associated antigen (TAA), with 80% showing two or more, indicating a strong potential for T-cell activation in immunotherapy.

Based on HLA expression analysis, at least 30% of RCC patients are eligible for monovalent immunotherapy and 41% for polyvalent immunotherapy, supporting the rationale for future vaccination trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous expression of T-cell activating antigens in renal cell carcinoma: implications for specific immunotherapy. Ringhoffer, M., Müller, CR., Schenk, A., et al.[2019]

Normal, tumor-distant renal T lymphocytes showed significantly higher activation and ability to kill tumor cells compared to tumor-infiltrating and peripheral blood T lymphocytes, indicating they are a better source for adoptive T-lymphocyte therapy in renal cell carcinoma.

Stimulation of these normal T lymphocytes with antigen-presenting cells and tumor cells, along with costimulation by anti-CD3 or interleukin-2, significantly enhanced their ability to lyse tumor cells, suggesting a promising approach for improving immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human accessory cells activate fresh, normal, tumor-distant T lymphocytes but not tumor-infiltrating T lymphocytes to lyse autologous tumor cells in a primary cytotoxic T lymphocyte assay in renal cell carcinoma. Kramer, G., Steiner, GE., Paiha, S., et al.[2019]

Chimeric antigen receptor (CAR) T-cells can target tumor cells without relying on HLA compatibility, allowing for the use of third-party donor-derived CAR T-cells, which could expand treatment access for more patients.

Creating a biobank of allogeneic CAR T-cells from healthy donors could streamline the manufacturing process, reduce costs, and ensure timely availability, but strategies must be developed to prevent immune rejection and toxicity in patients receiving these cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational Implications for Off-the-shelf Immune Cells Expressing Chimeric Antigen Receptors. Torikai, H., Cooper, LJ.[2021]

Allogeneic anti-CD3 antibody induced activated killer (CD3AK) cells demonstrated a significant inhibitory effect on the growth of human renal cell cancer (RCC) in SCID mice, leading to reduced tumor weight and slower tumor growth compared to control groups.

The study showed that CD3AK cells not only exerted a lethal effect on the OS-RC-2 renal cancer cell line but also enhanced the immune response in the mice, indicating their potential as a therapeutic option for RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of allogeneic CD3AK cells on transplanted human renal cell cancer in mice with severe combined immune deficiency. Ge, L., Shan, Z., Han, Q., et al.[2017]

Allogeneic hematopoietic stem cell transplantation can induce a graft-versus-tumor effect in metastatic renal cell carcinoma, with partial or complete responses observed in 20-40% of patients, although transplant-related mortality remains high at 10-20%.

The identification of specific T cell clones that target renal cancer antigens has paved the way for potential antigen-specific adoptive cell therapies, and combining these with targeted agents like sunitinib or bevacizumab may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic stem cell transplantation for renal cell carcinoma. Bregni, M., Herr, W., Blaise, D.[2022]

The study demonstrated the feasibility and safety of using ex vivo-expanded NK-92 cells as an allogeneic immunotherapy in 12 patients with refractory renal cell cancer and melanoma, with mild and transient toxicities observed during treatment.

One patient with renal cell cancer survived for 4 years post-infusion, indicating potential long-term benefits, while responses varied among other patients, highlighting the need for further research into this NK-cell based therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Arai, S., Meagher, R., Swearingen, M., et al.[2022]

Immunotherapy, particularly targeting renal cell tumor-associated antigens, is emerging as a promising alternative to traditional treatments like chemotherapy and radiotherapy for kidney carcinomas, which typically have a poor prognosis.

Recent trials have shown that cytokine-based therapies and T-cell activation strategies can lead to favorable clinical responses in some patients, highlighting the potential for improved outcomes as new antigens are identified for targeted immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of renal cell carcinoma. Gouttefangeas, C., Stenzl, A., Stevanović, S., et al.[2020]

CD70 CAR T cells have shown strong antitumor activity against renal cell carcinoma (RCC) in both cell lines and patient-derived mouse models, indicating their potential as an effective treatment option.

The development of fratricide-resistant CD70 CAR T cells, produced through TALEN-based gene editing, demonstrates both safety and efficacy, leading to the advancement of these cells into phase I clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma. Panowski, SH., Srinivasan, S., Tan, N., et al.[2023]

The RCC-26/CD80/IL-2 vaccine was well tolerated in a phase 1 trial involving 15 patients with metastatic renal cell carcinoma, with no serious side effects or autoimmunity observed, indicating its safety for use in this patient population.

While the vaccine did not lead to tumor regressions, it demonstrated potential for disease stabilization with a median survival of 15.6 months and induced immune responses against tumor antigens in most patients, suggesting it may be beneficial in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of allogeneic gene-modified tumor cell vaccine RCC-26/CD80/IL-2 in patients with metastatic renal cell carcinoma. Buchner, A., Pohla, H., Willimsky, G., et al.[2017]

The study involved 15 patients with metastatic renal cancer who received intratumoral injections of Allovectin-7, demonstrating that this method is safe and has minimal toxicity, with no significant adverse effects reported.

Gene expression of the HLA-B7 antigen was successfully achieved in 57% of patients, which may enhance the immune response against tumors, although no significant tumor regression was observed, suggesting further investigation in Phase II studies is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of direct intralesional gene transfer of HLA-B7 into metastatic renal carcinoma lesions. Rini, BI., Selk, LM., Vogelzang, NJ.[2020]

Citations

1. ir.allogene.com ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-provides-updated-phase-1-data-highlighting

Press Releases ALLO-316 is showing clear evidence of targeted antitumor activity in patients who had failed most or all approved therapies for advanced or metastatic renal ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4508

ALLO-316 in advanced clear cell renal cell carcinoma ... After a median follow-up of 6.8 months, a single infusion of ALLO-316 had manageable safety and encouraging antitumor activity in heavily pretreated patients.

3. urotoday.com urotoday.com/conference-highlights/asco-2025/asco-2025-kidney-cancer/160908-asco-2025-allo-316-in-advanced-clear-cell-renal-cell-carcinoma-updated-results-from-the-phase-1-traverse-study.html

ASCO 2025: ALLO-316 in Advanced Clear Cell Renal ... A single dose of ALLO-316 demonstrated a 31% confirmed ORR in patients with heavily-pretreated advanced or metastatic ccRCC. 4 of 5 responses ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38583184/

CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced ... These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70- targeted allogeneic CAR T cells.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04696731

NCT04696731 | Safety and Efficacy of ALLO-316 in ... The purpose of the TRAVERSE study is to assess the safety, efficacy, and cell kinetics of ALLO-316 in adults with advanced or metastatic clear cell renal cell ...

6. ir.allogene.com ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-announces-positive-phase-1-data

Allogene Therapeutics Announces Positive Phase 1 Data ... ALLO-316 is an AlloCAR T™ investigational product targeting CD70, which is highly expressed in renal cell carcinoma (RCC). CD70 is also ...