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Soo Park, MD
Soo Park, MD
Posted: Friday, July 26, 2024
Despite the documented efficacy of investigational unengineered tumor-infiltrating lymphocyte (TIL) therapy in patients with immune checkpoint inhibitor–resistant, unresectable or metastatic melanoma, its use requires systemic high-dose interleukin 2 (IL-2), which often causes high-grade toxicity. Rodabe Navroze Amaria, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues evaluated the use of OBX-115—an IL-2–sparing engineered TIL cell therapy that does not require co-administration of IL-2—in this patient population. The results of this study were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9515).
“OBX-115 regulatable engineered TIL-cell therapy was well tolerated and produced consistently deepening and durable responses, indicating that OBX-115 may mediate complete responses and durable clinical benefit in immune checkpoint inhibitor–resistant metastatic melanoma without high-dose IL-2,” the investigators concluded.
This phase I study enrolled nine patients with immune checkpoint inhibitor–resistant metastatic melanoma to receive an infusion of OBX-115 followed by 7 days of once-daily acetazolamide (diuretic). OBX-115 was engineered from the patient’s tumor tissue and was administered after lymphodepletion with cyclophosphamide and fludarabine. Acetazolamide re-dosing was permitted for nonresponders.
The median number of prior therapy lines was three. OBX-115 was successfully engineered for all patients, including five core needle biopsies. The infusion contained a high proportion of CD8-positive cells (≥ 96%) with very low PD-1 expression (< 1%). At the median follow-up of 12 weeks, the objective response rate was 50% for six patients, consisting of two complete responses, one partial response, and three cases of stable disease; all responses were ongoing.
No dose-limiting toxicities were reported. Grade 3 nonhematologic treatment-emergent adverse events were reported in two patients, but no grade 4 events were observed. New metastatic disease in the liver was identified in one patient, whose disease progressed at week 24. Brain metastasis was not reported in any patient.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
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