FDA Clears IND Application for TIL Therapy OBX-115 for R/R Metastatic Melanoma

The FDA has cleared the investigational new drug application for a phase 1 clinical study (NCT05470283) of OBX-115, an investigational tumor infiltrating lymphocyte (TIL) therapy developed in a collaboration between Obsidian Therapeutics and the University of Texas MD Anderson Cancer Center for the treatment of relapsed/refractory metastatic melanoma.¹

In preclinical studies, OBX-115 demonstrated improved TIL persistence, potency, and tumor control compared with unengineered TILs. Additionally, OBX-115 does not require simultaneous treatment with interleukin-2 therapy, a major drawback of most other TILs due to its toxicity.

“There is a significant opportunity to improve the standard of care in melanoma, especially in later line patients and those who have not responded well to immune checkpoint therapies,” Rodabe Amaria, MD, associate professor of Melanoma Medical Oncology at MD Anderson and principal investigator of the OBX-115 study, said in a statement.¹ “Preclinical studies suggest OBX-115 has the potential to show efficacy in these patients... We look forward to continuing our collaboration with Obsidian to advance this novel therapy for our patients in need of new treatment options.”

The single-arm, open-label clinical trial will enroll male and female patients aged 18 and older that have a diagnosis of unresectable stage III or stage IV metastatic melanoma with lesion(s) that can be resected for the generation of TILs. Patients must be relapsed and/or refractory to immune checkpoint inhibitor therapy and have an ECOG Performance status of 0-1. Female patients of childbearing potential must have a negative serum pregnancy test prior to treatment. Patients with uncontrolled intercurrent illnesses, those on chronic steroid therapy for primary immunodeficiency, or who have a history of organ or hematopoietic stem cell transplant, or who have undergone chemotherapy within 2 weeks prior to TIL harvest, will be excluded from the study.

The study is expected to enroll 30 participants. Patients will undergo a chemotherapy conditioning regimen prior to receiving the drug combination, which will include intravenous OBX-115, oral acetazolamide, and intravenous cyclophosphamide, furosemide, mesna, and fludarabine phosphate. The primary end point will be to assess the safety and tolerability of the treatment according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 in order to determine a recommended dose for phase 2. Secondary end points will include evaluations of efficacy based on the overall response rate, duration of response, and progression-free survival. The pharmacokinetic profile of acetazolamide administered in combination with OBX-115 and the incidence and prevalence of the OBX-115 therapy’s immunogenicity will also be examined. Exploratory end points will include examinations of the correlation of OBX-115 kinetics with clinical end points and an evaluation of overall survival.

“The FDA clearance of the IND application for OBX-115 represents an important milestone for Obsidian and our colleagues at MD Anderson, and it is the result of years of commitment to developing a novel class of engineered TILs,” Paul Wotton, PhD, chief executive officer of Obsidian Therapeutics, added to the statement.¹ “We believe OBX-115 therapy has the potential to significantly transform the treatment landscape for patients, bringing broader access to TILs with the elimination of concomitant IL2 therapy, and the potential to achieve improved clinical outcomes.”

The clinical trial is expected to begin on August 22, 2022, and its estimated completion date is April 1, 2027.

REFERENCES

MD Anderson and Obsidian Therapeutics announce FDA Clearance of IND application for novel TIL therapy OBX-115. News release. Obsidian Therapeutics, Inc. July 21, 2022. https://obsidiantx.com/news-releases/md-anderson-and-obsidian-therapeutics-announce-fda-clearance-of-ind-application-for-novel-til-therapy-obx-115/