MINIMALLY INVASIVE TUMOR TISSUE PROCUREMENT IS FEASIBLE FOR CLINICAL MANUFACTURING OF OBX-115 ENGINEERED TUMOR-INFILTRATING LYMPHOCYTES (TIL)

• Published in: Cytotherapy (Oxford, England) Vol. 26; no. 6; pp. S154 - S155
• Main Authors: Bernatchez, C., Balasubramanian, P., Cressman, E.N., Weiser, R., Fisher, S.B., Chun, Y., Forget, M., Sakellariou-Thompson, D., Lai, I., Fulbright, O., Adlerz, K., Khatiwala, C., Wilmes, G., Hari, P., Ramsingh, G., Prabhakar, P., Amaria, R.N.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-06-2024
• Subjects: Genetic engineering; Melanoma; TIL cell therapy; Genetic engineering; TIL cell therapy; Melanoma
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2024.03.300

TIL cell therapy is a promising investigational treatment for patients (pts) with advanced solid tumors. As an autologous adoptive T-cell therapy, a portion of the pt's tumor tissue is used as the starting material to manufacture the TIL product. Although tumor tissue procurement (TTP) is typically surgical, minimally invasive TTP using an outpatient core needle biopsy (CNB) procedure may avoid surgical morbidity, reduce cost, and alleviate scheduling challenges. Herein we describe manufacturing success, phenotype, and clinical outcome of OBX-115, an engineered TIL expressing membrane-bound IL15 (mbIL15), manufactured using tissue obtained by minimally invasive and surgical TTP in a Phase 1 first-in-human study (NCT05470283).
Eligible pts underwent TTP to provide starting material for OBX-115 manufacturing (multiple ≥1.5-cm length CNBs or ≥1.5-cm diameter surgical tissue). TIL were expanded ex vivo from tumor tissue and transduced with retroviral vector to express mbIL15 as a fusion protein with a drug-responsive domain to allow pharmacologic regulation of mbIL15 cell-surface expression using the FDA-approved small-molecule drug acetazolamide.
Of the first 6 pts infused with OBX-115, 5 had minimally invasive TTP (CNB) and 1 had surgical TTP. All CNBs were performed without general anesthesia. CNB tumor tissue (range, 3–9 cores) was procured from lymph node (n=2), abdominal soft tissue (n=1), chest wall soft tissue (n=1), and liver (n=1). OBX-115 dose manufactured from CNB ranged from 9.6 × 109 to 163 × 109 cells (infused dose was capped at protocol-specified maximums). The infusion products were predominantly CD3+ (range, 97%–100%) and CD8+ (range, 95.9%–99.5%). Regardless of TTP method, OBX-115 met cell dose and phenotype requirements for infusion. Two pts treated with OBX-115 manufactured from CNB experienced durable complete remission (CR), ongoing at 22 and 52 weeks post-infusion (Dec 1 2023 datacut).
In summary, OBX-115 was successfully manufactured from CNB and surgical tumor tissue. Regardless of TTP method, OBX-115 cell dose and phenotype met requirements for infusion. Notably, 2 pts who received OBX-115 manufactured by CNB tumor tissue achieved durable CRs. These results support the manufacturing feasibility and potential efficacy of OBX-115 engineered TIL cell therapy generated using minimally invasive TTP, and further support a potential outpatient TTP option that may increase the pt population eligible to receive TIL cell therapy.