ALLO-316 Shows 50% Response Rate in CD70-Positive RCC in Phase 1 Trial

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Single infusion of ALLO-316 demonstrated an overall response rate of 50% and confirmed response (CR) rate of 33% among patients with CD70-positive renal cell carcinoma (RCC) with tumor proportion score (TPS) of greater than 50%, according to findings from the phase 1 TRAVERSE trial (NCT04696731).¹

Data from the study are being presented at both the 2024 International Kidney Cancer Symposium (IKCS) and the Society for Immunotherapy of Cancer's (SITC) annual meetings. As of October 14, 2024, the study’s data cutoff, 39 patients had been enrolled, 26 of whom had confirmed CD70-positive RCC and were evaluable for efficacy outcomes. The median time from enrollment to the start of therapy was 5 days.

Patients with a TPS of ≥50% made up most patients in the study with advanced or metastatic RCC. Of the patients with a TPS score of greater than 50%, 76% of patients (16/21) had a reduction in tumor burden. Additionally, 33% of patients (2/6) with high TPS who received the phase 1b expansion regimen showed durable responses ongoing at 4 months or more.

“We are encouraged with results like ALLO-316 and some others. We are getting into that new era where we will, hopefully soon in the coming few years, be able to establish some sort of new standards,” Samer A. Srour, MD, assistant professor, Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, told Targeted Oncology^TM in an interview.

“ALLO-316, the leading ‘off-the-shelf’ [chimeric antigen receptor (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 antitumor 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, executive vice president of research and development and chief medical officer of Allogene Therapeutics, in a press release. “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.”

The ongoing phase 1 trial is evaluating ALLO-316 for the treatment of patients with solid tumors. Patients with advanced or metastatic RCC who have progressed following treatment with an immune checkpoint inhibitor and VEGF-targeting therapy.²

Additional findings from the study showed that ALLO-316 led to a manageable safety profile.1 The most common all-grade adverse events observed among patients included cytokine release syndrome, with only 1 that was grade 3 or higher, fatigue (59%), neutropenia (56%), decreased white blood cell count (54%), anemia (51%), and nausea (51%). Immune effector cell-associated neurotoxicity syndrome was seen in 8% of patients. Additionally, no graft-vs-host disease occurred.

There were 2 dose-limiting toxicity (DLT) events reported in the study, including autoimmune hepatitis and cardiogenic shock, each of which were seen in 2 separate patients given FC300 plus ALLO-647 lymphodepletion and dose level 2 of ALLO-316.

Three treatment-related adverse events were observed. The first was cardiogenic shock, which was 1 of the 2 DLTs in the trial. The second was sepsis due to multidrug resistant Klebsiella pneumoniae in a patient treated with dose level 4 of ALLO-316. This patient had a prior history of muscle abscess and bacteremia from the same pathogen and was on anakinra and dexamethasone for managing hyperinflammation. Finally, failure to thrive 16 months after ALLO-316 treatment was noted in a patient with stable disease at 12 months, but no follow-up imaging was available to assess disease progression prior to death.

The presentations at IKCS and SITC will include evidence of CAR T-cell activity and antitumor efficacy in 26 patients with RCC tumors known to be CD70-positive who were evaluable for efficacy outcomes.

REFERENCES:

1. 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, Inc. November 7, 2024. Accessed November 7, 2024. https://tinyurl.com/3m4h7s3x

2. Safety and efficacy of ALLO-316 in subjects with advanced or metastatic clear cell renal cell carcinoma (TRAVERSE). ClinicalTrials.gov. Updated November 1, 2024. Accessed November 7, 2024. https://clinicaltrials.gov/study/NCT04696731