ALLO-316 shows encouraging CAR activity in advanced ccRCC

ALLO-316 demonstrated initial clinical activity while maintaining a manageable safety profile in patients with relapsed or refractory advanced or metastatic clear cell renal cell carcinoma (ccRCC), according to updated data from the phase 1 TRAVERSE trial (NCT04696731) presented at 2024 International Kidney Cancer Symposium: North America in Louisville, Kentucky.¹

Additional data from the study are expected to be reported in mid-2025.

Last month, the FDA granted ALLO-316 a Regenerative Medicine Advanced Therapy designation for patients withCD70-positive advanced or metastatic RCC who have received prior immune checkpoint inhibitor and VEGF-targeting therapy.² ALLO-316 was also previously granted a fast track designation by the FDA for the same indication in March 2022.³

“ALLO-316, the leading “off-the-shelf” CAR T product candidate currently in development for solid tumors, continues to show remarkable potency in the TRAVERSE trial. Data from the phase 1 study, demonstrating significant anti-tumor activity in patients with metastatic disease resistant to multiple therapeutic classes, even with standard lymphodepletion, potentially marks a major advancement in the field,” said Zachary Roberts, MD, PhD, EVP, Research and Development and Chief Medical Officer of Allogene Therapeutics, in a news release on the data.⁴ “The unprecedented cell expansion and persistence driven by CD70 CAR-intrinsic Dagger technology, along with strong evidence of tumor infiltration by CAR T cells, highlights the distinctive features of ALLO-316. We believe these findings from our phase 1 trial lay the groundwork for a new generation of allogeneic cell therapies.”

For the trial, patients received escalating dose levels of ALLO-316 (40 to 240×106 allogeneic CAR+ T cells) following lymphodepletion (fludarabine and cyclophosphamide +/- ALLO-647, an anti-CD52 monoclonal antibody). Reported data also encompassed the ongoing phase 1b expansion cohort, exploring ALLO-316 at dose level 2 (DL2; 80M CAR T cells) following a lymphodepletion regimen of standard FC500 (fludarabine (30 mg/m2/day) and cyclophosphamide (500 mg/m2/d) for 3 days.

At the time of data report, 39 patients were enrolled in the study. Of these, 34 were evaluable for disease outcomes, and 26 were confirmed to have CD70-positive RCC.

Data showed a best overall response rate of 50% and a confirmed response rate of 33% among patients with a CD70 tumor proportion score (TPS) of 50% or higher who received a single infusion of ALLO-316 at DL2. Additionally, 76% of patients with a CD70 TPS of at least 50% achieved a reduction in tumor burden. Among patients with a high TPS, 33% (2/6) showed an ongoing durable response at 4 months or longer.

ALLO-316 also demonstrated a manageable safety profile, according to the authors. The most common all-grade AEs were cytokine release syndrome (62%; all low grade except 1 grade 3), fatigue (59%), neutropenia (56%), leukopenia (54%), nausea (51%), and anemia (51%). The study also reported 2 dose limiting toxicity events due to autoimmune hepatitis and cardiogenic shock.

Immune effector-cell associated neurotoxicity syndrome occurred in 8% of patients. No instances of graft-versus-host disease were observed. Some patients experienced effector cell-associated HLH-like syndrome; these events were managed with ruxolitinib.

Overall, TRAVERSE is a first-in-human, dose-escalation, multicenter trial of ALLO-316, which is a novel off-the-shelf, HLA-unmatched, CD70-targeting CAR T-cell treatment under investigation for patients with RCC. The trial is assessing ALLO-316 at 4 cell dose levels: DL1=40M cells, DL2= 80M cells, DL3=120M cells, and DL4= 240M cells.

At the time of data cutoff, 39 patients had been enrolled in the trial. The median age was 62 years, and 87% of patients were male. The median number of prior therapies was 3.

All patients included in the trial had advanced or metastatic clear cell RCC with at least 1 measurable lesion and an ECOG Performance Score of 0 or 1. Prior treatment with an immune checkpoint inhibitor and VEGF-targeted therapy was required.⁵ The median time from enrollment in the trial to the start of therapy was 5 days.

The primary end point for the study is the rate of dose-limiting toxicities, as assessed at 28 days following infusion with ALLO-316.

According to Allogene, the study plans to include 20 additional patients in the phase 1b expansion cohort. Data from this cohort are expected to be reported in mid-2025.

Overall, the authors concluded, “Preliminary analyses in CD70+ tumors provided encouraging evidence of CAR activity, supporting further evaluation of ALLO-316 in CD70+ ccRCC and other CD70+ malignancies.”

References

1. Srour SA, Chahoud J, Drakaki A, et al. TRAVERSE: Updated safety and efficacy of ALLO-316 in advanced/metastatic clear cell renal cell carcinoma (ccRCC). Presented at: 2024 International Kidney Cancer Symposium: North America. November 7-9, 2024. Louisville, Kentucky. Abstract F2

2. Allogene Therapeutics receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for ALLO-316, an AlloCAR T investigational product for adult patients with advanced or metastatic renal cell carcinoma (RCC). News release. Allogene Therapeutics. October 29, 2024. Accessed November 8, 2024. https://www.globenewswire.com/en/news-release/2024/10/29/2970809/0/en/Allogene-Therapeutics-Receives-FDA-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-for-ALLO-316-an-AlloCAR-T-Investigational-Product-for-Adult-Patients-with-Advanced-or-Met.html

3. Allogene Therapeutics receives FDA Fast Track Designation for its first solid tumor candidate, ALLO-316 in the treatment of renal cell carcinoma. News release. Allogene Therapeutics. March 10, 2022. Accessed November 8 ,2024. https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-receives-fda-fast-track-designation-its

4. Allogene Therapeutics announces positive phase 1 data demonstrating the potential of ALLO-316 in heavily pretreated patients with advanced renal cell carcinoma at SITC and IKCS. News release. Allogene Therapeutics. November 7, 2024. Accessed November 8, 2024. https://www.globenewswire.com/en/news-release/2024/11/07/2976851/0/en/Allogene-Therapeutics-Announces-Positive-Phase-1-Data-Demonstrating-the-Potential-of-ALLO-316-in-Heavily-Pretreated-Patients-with-Advanced-Renal-Cell-Carcinoma-at-SITC-and-IKCS.html

5. Safety and efficacy of ALLO-316 in subjects with advanced or metastatic clear cell renal cell carcinoma (TRAVERSE). ClinicalTrials.gov. Last updated November 1, 2024. Accessed November 8, 2024. https://clinicaltrials.gov/study/NCT04696731