Abstract CT244: Trial in progress: Phase 1/2 study of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced solid tumors

Abstract Background: Non-engineered TIL cell therapy was recently approved for patients with immune checkpoint inhibitor (ICI)-resistant melanoma (Chesney JITC 2022) and shows promising efficacy in non-small cell lung cancer ([NSCLC]; Creelan Nat Med 2021, Schoenfeld Cancer Discov 2024), but has a treatment-related mortality rate of 7.5% in melanoma and requires co-administration of systemic high-dose IL2, with well-described high-grade toxicity. OBX-115 TIL are expanded from patient tumor tissue and engineered with a transgene to express membrane-bound human IL15 (mbIL15), regulated by acetazolamide (ACZ), eliminating the need for IL2. A first-in-human single-institution study evaluating the safety of OBX-115 in metastatic melanoma has completed enrollment (NCT05470283; Amaria ASCO 2024). The current study (NCT06060613) is enrolling patients with melanoma and NSCLC at multiple US sites using centralized manufacturing. Methods: This phase 1/2, single-arm, open-label, nonrandomized, multicenter study will assess the safety, tolerability, and efficacy of the OBX-115 engineered autologous TIL cell therapy regimen in patients with unresectable Stage IIIC-IV metastatic melanoma (excluding uveal) with radiographic progression after systemic therapy containing PD-1-targeted ICI (≤2 prior lines; neoadjuvant/adjuvant considered prior line if progressed during treatment or within ≤12 weeks of last dose) OR metastatic NSCLC previously treated with an approved systemic therapy for metastatic disease (including an ICI-based regimen and/or targeted therapy where applicable) and progressed, no longer deriving benefit, or unable to continue due to treatment intolerance. Patients may have treated and asymptomatic brain metastases and must have ECOG PS of 0 or 1, life expectancy >∼6 months, ≥1 lesion suitable for OBX-115 manufacturing, and ≥1 RECIST v1.1-measurable lesion remaining after tumor tissue procurement. Primary objectives of Phase 1 are to characterize safety and tolerability and identify a recommended Phase 2 dose of OBX-115 + ACZ; Phase 2 will evaluate efficacy of the regimen (ORR using RECIST v1.1 per investigator). Melanoma RP2D has been determined and is in Phase 2; NSCLC is in Phase 1. Cryopreserved OBX-115 is generated from the patient’s own tumor tissue procured by surgical excision or core needle biopsy and is infused after standard- or low-dose lymphodepletion (cyclophosphamide and fludarabine) based on clinical status and prior treatments. No IL2 is administered. ACZ is administered at cohort-defined doses once daily starting day of OBX-115 infusion for ≤14 days (split into two ≤7-day periods within 28 days), with additional ACZ dosing for ≤7 days at weeks 5, 11, 17, and 23, or upon progression when new anticancer therapy is not immediately warranted. Eight sites are open and recruiting, with additional sites being activated. Citation Format: Alexander N. Shoushtari, Adam J. Schoenfeld, Kai He, Jason A. Chesney, Juan Carlos Varela, Justin T. Moyers, Gino K. In, Yazan Samhouri, Rodabe N. Amaria, Parameswaran Hari, Giridharan Ramsingh, Camille Renard, Prakash Prabhakar, Lauren Mclaughlin, Mercay Reuter, Allison Betof Warner. Trial in progress: Phase 1/2 study of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT244.