2024 World Conference on Lung Cancer (WCLC) - Posters-P4.11D.03 Trial in Progress: Phase 1/2 Study of OBX-115 Engineered Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy in Patients with Advanced Solid Tumors

P4.11D.03 Trial in Progress: Phase 1/2 Study of OBX-115 Engineered Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy in Patients with Advanced Solid Tumors

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Immune checkpoint inhibitors have significantly improved treatment for melanoma and non-small cell lung cancer (NSCLC), but long-term survival remains a challenge for many patients. Lifileucel, a non-engineered tumor-derived autologous T-cell immunotherapy, has shown promising results in melanoma patients previously treated with anti–PD-1 therapy, yielding an objective response rate of 31.5%. However, it is associated with a treatment-related mortality rate of 7.5%. Another promising TIL therapy, OBX-115 (cytoTIL15™), engineered with membrane-bound IL15 activated by acetazolamide (ACZ) to bypass the toxic interleukin 2 requirement, has shown enhanced efficacy in preclinical studies and favorable characteristics, including a high proportion of CD8 T cells.<br /><br />The ongoing Agni-01 trial is assessing OBX-115 in advanced solid tumors, focusing on safety, efficacy, and tolerability in Phase 1 (dose-escalation) and Phase 2. Early human trials of OBX-115 demonstrate a 44% objective response rate and 75% six-month progression-free survival rate, with a unique safety profile.<br /><br />This study is significant for patients resistant to existing therapies, particularly those with advanced melanoma or NSCLC. Participants must have measurable disease after tissue procurement, stage IIIC, IIID, or IV unresectable melanoma, or metastatic NSCLC with progression post systemic therapy. The trial utilizes centralized manufacturing for OBX-115 production, requiring minimally invasive tumor tissue procurement for TIL generation. Patients receive no IL2, reducing associated toxicity risks and making the treatment more accessible.<br /><br />Funded by Obsidian Therapeutics, the trial underscores ongoing efforts to advance cancer immunotherapy through innovative TIL engineering and drug combinations. This approach may shift treatment paradigms, offering new hope for extending survival in challenging cancer cases.

Asset Subtitle

Adam Schoenfeld

Meta Tag

Speaker Adam Schoenfeld

Topic Metastatic NSCLC – Immunotherapy

Keywords

immune checkpoint inhibitors

melanoma

non-small cell lung cancer

lifileucel

T-cell immunotherapy

OBX-115

Agni-01 trial

tumor-infiltrating lymphocytes

cancer immunotherapy

Obsidian Therapeutics