Allogene Therapeutics’ ALLO-329 Cleared by FDA for Phase 1 Clinical Trial in Rheumatology Indications
The planned phase 1 RESOLUTION study will include patients with systemic lupus erythematosus, lupus nephritis, idiopathic inflammatory myopathies, and systemic sclerosis.
Allogene Therapeutics’ ALLO-329, an investigational allogeneic chimeric antigen receptor T-cell (CAR-T) therapy, has received clearance of an investigational new drug (IND) application from the FDA for a phase 1 rheumatology basket study.1
In light of the IND clearance, Allogene intends to go forward with plans for RESOLUTION, a phase 1 clinical trial (NCT identifier pending) for ALLO-329 in systemic lupus erythematosus, lupus nephritis, idiopathic inflammatory myopathies, and systemic sclerosis. The study, which Allogene anticipates will be launch in the middle of this year, will include 2 different lymphodepletion arms. In one arm patients will receive cyclophosphamide alone for lymphodepletion and in the other no lymphodepletion regimen will be used.
Notably, ALLO-329 targets both CD19+ B-cells and CD70+ activated T-cells, with the intention of eliminating dysfunctional cells of both types. Furthermore, the CAR-T product utilizes the company’s Dagger technology, which is intended to reduce or eliminate the need for lymphodepletion by making the CAR-T more resistant to rejection by the patient’s immune system. Allogene stated that ALLO-329 may be able to be manufactured at a scale of 60,000 doses annually. In addition, the potential to reduce or circumvent the need for lymphodepletion prior to treatment may allow more patients to be eligible for the product.
“A year ago, we unveiled the concept of ALLO-329, an allogeneic CAR-T product specifically designed to address the unique challenges faced by patients with autoimmune diseases,” David Chang, MD, PhD, the president, CEO, and cofounder of Allogene, said in a statement.1 “Today, with the FDA’s clearance of our IND, that vision has become a reality, achieved at an extraordinary pace thanks to Allogene’s unparalleled expertise in research, manufacturing, and clinical development. Demonstrating the power of an allogeneic CAR-T to reset the immune system, combined with the ability of our Dagger technology to reduce or eliminate lymphodepletion, could represent a transformative step forward. Successful proof-of-concept in this basket study has the potential to not only validate our best-in-class approach but also paves the way for expanding into a broad range of autoimmune indications beyond rheumatology.”
In addition to ALLO-329, Allogene currently has several other CAR-T therapies in clinical stage development. One of these is ALLO-316, an allogeneic CD70-directed CAR-T therapy being evaluated for the treatment of advanced or metastatic renal cell carcinoma (RCC) treated in the phase 1 TRAVERSE clinical trial (NCT04696731).2 Data from this trial were recently presented at the Society for Immunotherapy of Cancer’s (SITC) 39th Annual Meeting, held November 6-10, 2024, in Houston, Texas. The study’s efficacy findings covered 26 patients who had confirmed CD70-positive RCC and were evaluable as of the October 14, 2024 data cutoff. Among 8 patients who were treated at dose-level 2 (80 million CAR T-cells) after a standard FC500 [fludarabine (30 mg/m2/day) and cyclophosphamide (500 mg/m2/d) for 3 days] lymphodepletion regimen, which was used as the dose for the phase 1b expansion cohort, the best overall response rate (ORR) was 38% (3/8).
“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,” Zachary Roberts, MD, PhD, EVP, research and development and chief medical officer of Allogene, said in a November 2024 statement.2 “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. 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.”
