Allogene Therapeutics presents interim Phase 1 data on ALLO-316

Allogene Therapeutics presented interim data from its Phase 1 TRAVERSE trial of ALLO-316, the Company’s first AlloCAR T investigational product candidate for solid tumors, in an oral presentation at the American Association for Cancer Research Annual Meeting in Orlando, Florida. The presentation follows the release of initial ALLO-316 data reported at the Company’s R&D Showcase event in November 2022. The ongoing Phase 1 TRAVERSE study is enrolling patients with advanced or metastatic renal cell carcinoma who have progressed on standard therapies that include an immune checkpoint inhibitor and a VEGF-targeting therapy. Emerging data from this trial have demonstrated the potential of an AlloCAR T to treat CD70 expressing RCC. In this trial, ALLO-316 showed early anti-tumor activity with deepening responses over time. As of the March 23, 2023 data cutoff, 19 patients were enrolled in the Phase 1 trial, 10 of whom had RCC confirmed to express CD70. The median time from enrollment to the start of therapy was five days. In the ongoing dose escalation phase of the TRAVERSE trial, patients will receive lymphodepletion followed by ALLO-316 at one of four cell dose levels. The data reported to date is primarily from the DL1 and DL2 cohorts. Anti-tumor activity was primarily observed in patients with tumors confirmed to express CD70. Among 18 patients evaluable for efficacy, the disease control rate was 89%. In the 10 patients whose tumors were known to express CD70, the disease control rate was 100%, which included three patients who achieved partial remission. The longest response lasted until month eight. There was a trend toward greater tumor shrinkage in patients with higher levels of CD70 expression. There were 19 patients evaluable for safety. To date, ALLO-316 has demonstrated an adverse event profile generally consistent with autologous CAR T therapies. One dose-limiting toxicity of Grade 3 autoimmune hepatitis occurred in the second dose level. Cytokine release syndrome was all low-grade with the exception of one Grade 3. Neurotoxicity, which is now defined more broadly, was generally low grade and reversible with most events being fatigue or headache. There were no cases of immune effector cell-associated neurotoxicity syndrome. Infections occurred in eight patients of which four were Grade 3+ including one Grade 5 respiratory failure due to Covid-19 infection deemed unrelated to study treatment. Grade 3+ prolonged cytopenia was observed in three patients. There were no cases of graft-versus-host disease. The Dagger technology, which is a feature of ALLO-316, is designed to resist rejection of AlloCAR T cells by the host immune cells, thereby supporting expansion and enabling a prolonged window of persistence during which AlloCAR T cells can target and destroy cancer cells. Initial translational data from the TRAVERSE trial demonstrates the suppression of host T cells and marked peak expansion of ALLO-316 despite the relatively low cell doses tested. In addition to ALLO-316, the Company plans to deploy Dagger technology to potentially enhance the persistence and activity of next generation AlloCAR T products.