CLTR-03 IMPACT-MET: A PHASE I STUDY TO ASSESS SAFETY AND FEASIBILITY OF IL-8 RECEPTOR MODIFIED, PATIENT-DERIVED, ACTIVATED CD70 CAR T CELL THERAPY IN ADULTS WITH BRAIN METASTASES FROM PRIMARY CANCERS

Abstract

Abstract Introduction Brain metastases (BM) occur in 10%–20% of adults with malignancies. Current therapeutic options are limited in the central nervous system by poor blood brain barrier penetration, immune resistance mechanisms, and immunosuppressive tumor microenvironment. Our team has identified CD70 as an immunotherapeutic target common to glioblastoma and primary lung cancer BM. CD70 contributes significantly to immunosuppression and poor prognosis across various malignancies, including CNS tumors. Standard treatment of brain metastases commonly involves radiation, which induces upregulation of IL-8 release within the tumor bed. By engineering the CAR to target IL-8 receptor, this radiation-induced signal can be leveraged as a “GPS homing cue”, enhancing T cell trafficking to CD70-expressing tumor cells. Preclinical studies demonstrate that 8R-70CAR T cells not only improve antitumor response but also establish durable immune memory responses. Methods We will enroll 12 newly diagnosed or recurrent patients with BM from primary lung cancer whose tumors express CD70 in a Phase I, open-label, single-arm study evaluating the safety and feasibility of IL-8 receptor-modified, patient-derived, activated CD70 CAR T cells. The study will also determine the maximum tolerated dose for adult patients using a BOIN dose-escalation design. Feasibility will be evaluated based on the ability to manufacture and safely infuse 8R-70CAR-T-cell in 66.7% of enrolled patients; and safety will be assessed by the incidence and severity of adverse events, serious adverse events, and dose-limiting toxicities. 8R-70CAR T-cell therapy is under investigation in a Phase I clinical trial for adult glioblastoma patients. Safe dose levels determined in the glioblastoma trial will guide the starting dose for this BM trial. Results This study is not yet recruiting. Conclusion This study will evaluate the safety and feasibility of 8R-70CAR T cells in BM patients and may inform on the future development of 8R-70CAR T cell therapy in this population.