amsokigene autoleucel (OBX-115) / Obsidian, UT MD Anderson Cancer Center - LARVOL DELTA

Recent Advances in Tumor-Infiltrating Lymphocyte Therapy for Melanoma. (PubMed, Curr Treat Options Oncol) - "We then review current clinical evidence for conventional TIL products, including lifileucel, TM001, LM103, HS-IT101, and GC101, highlighting their efficacy and safety profiles...In addition, advances in genetically engineered TILs, such as OBX-115, KSQ-001EX, and IOV-4001, are reviewed...Challenges and future directions of TIL therapy in melanoma are also discussed. Overall, TIL therapy constitutes a rapidly evolving and clinically potent treatment modality for melanoma."

Biomarker • IO biomarker • Journal • Review • Tumor-infiltrating lymphocyte • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • IL2

Top advances of the year in autologous cellular therapy in melanoma and solid tumors. (PubMed, Cancer) - "Lifileucel, the first Food and Drug Administration-approved tumor-infiltrating lymphocyte (TIL) therapy for advanced melanoma, demonstrated durable efficacy in the 5-year analysis of the C-144-01 trial, with an objective response rate (ORR) of 31.4% and prolonged responses in a heavily pretreated population...Preferentially expressed antigen in melanoma (PRAME)-targeted T-cell receptor (TCR) T-cell therapy (anzu-cel, IMA203) showed promising activity in a phase 1 study, with ORR of approximately 50% in checkpoint inhibitor refractory melanoma, durable responses, and manageable toxicity, validating PRAME as a high value target across multiple tumor types...OBX-115, an IL-2 independent TIL platform expressing membrane-bound IL-15 regulated by acetazolamide, demonstrated early clinical activity with ORR of 67% in initial phase 1 data...Finally, afamitresgene autoleucel (afami-cel), a MAGE-A4 directed TCR-T therapy, showed durable efficacy in synovial sarcoma and expanding..."

Journal • Review • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • IL15 • MAGEA4 • PRAME

Trial in progress: Agni-01 phase 2 cohort of OBX-115 tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced (adv) melanoma (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor

OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients (pts) with immune checkpoint inhibitor (ICI)–resistant advanced melanoma: Phase 1 results of the Agni-01 multicenter study. (ASCO 2025) - P1, P1/2 | "Funded by Obsidian Therapeutics Clinical Trial Registration Number: NCT06060613 Background: OBX-115 TIL are engineered to express mbIL15 regulated by the FDA-approved small-molecule drug acetazolamide (ACZ), abrogating the need for toxic high-dose IL2 after TIL infusion... Early data support clinical benefit (RP2D ORR 67%, DCR 100%) of OBX-115 regulatable engineered TIL cell therapy in the absence of IL2, including with outpatient low-dose LD. The safety profile is highly differentiated, without TRM, ICU transfer, or high-grade CRS. ACZ redosing is well-tolerated and offers an opportunity to deepen responses by inducing re-expression of mbIL15 on engrafted OBX-115 TIL, a unique capability among adoptive cell therapies."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • P1 data • Tumor-infiltrating lymphocyte • Heart Failure • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15 • IL6

OBX-115, an interleukin 2 (IL2)-sparing engineered tumor-infiltrating lymphocyte (TIL) cell therapy, in patients (pts) with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma. (ASCO 2024) - P1, P1/2 | "OBX-115 autologous engineered TIL cell therapy does not require co-administration of IL2 due to its regulatable expression of membrane-bound IL15 (mbIL15) using the FDA-approved small-molecule drug acetazolamide (ACZ) to provide cytokine support for TIL expansion and persistence...After lymphodepletion (cyclophosphamide, fludarabine), pts receive OBX-115 followed by ACZ once daily for up to 7 days; ACZ redosing (up to 7 days) is permitted at Wk 6 for non-responders... OBX-115regulatableengineeredTIL cell therapy was well-tolerated and produced consistently deepening and durable responses, indicating that OBX-115 may mediate CRs and durable clinical benefit in ICI-resistant metastatic melanoma without high-dose IL2. OBX-115 investigation continues in this and an ongoing Phase 1/2 multicenter study (NCT06060613)."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • Tumor-infiltrating lymphocyte • Hepatology • Melanoma • Oncology • Pain • Solid Tumor • CD69 • CD8 • ENTPD1 • IL15 • IL2 • PD-1

OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients with advanced melanoma that has progressed on/after immune checkpoint inhibitors (ICI): Phase 2 results. (ASCO 2026) - P1/2 | "Clinical Trial Registration Number: NCT06060613 Background: OBX-115 TIL are engineered to express mbIL15 under regulatory control of the small-molecule drug acetazolamide (ACZ); this engineering abrogates the need for toxic high-dose IL2 cytokine support after TIL infusion. OBX-115 TIL cell therapy at RP2D demonstrated encouraging efficacy in 2/3L advanced non-uveal melanoma, an area of unmet medical need. Unique aspects of the OBX-115 regimen, such as low-dose LD, ACZ-inducible mbIL15 expression, and CNB-enabled manufacturing, were associated with manageable side effects and compare favorably with other adoptive TIL approaches. Data support continued investigation of OBX-115 in the ongoing phase 2 portion of Agni-01 and planned registrational study."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • P2 data • Tumor-infiltrating lymphocyte • Eye Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15

A phase 1/2 study to investigate the safety and efficacy of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced solid tumors. (ASCO 2024) - P1, P1/2 | "OBX-115 TIL are engineered to express membrane-bound IL15 (mbIL15) under dose-dependent regulation using acetazolamide (ACZ), an FDA-approved small-molecule diuretic, avoiding the need for high-dose IL2...Cryopreserved OBX-115 is generated from the pt's own tumor tissue procured by surgical excision or core needle biopsy, and is infused after standard- (5 days) or low-dose (4 days) lymphodepletion (cyclophosphamide and fludarabine), based on clinical status...3. Creelan Nat Med 2021; Schoenfeld SITC 2021."

Clinical • IO biomarker • Metastases • P1/2 data • Tumor-infiltrating lymphocyte • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15

Obsidian Therapeutics Announces First Patient Enrolled in the Registration-enabling Cohort of Phase 1/2 Agni-01 Study Evaluating Amsoki-cel (OBX-115) in Advanced Melanoma (Businesswire) - "...'We anticipate reporting topline data from the registration-enabling cohort by year-end 2027'....The single-arm registration-enabling cohort is part of the ongoing Agni-01 study (NCT06060613), which is a multicenter Phase 1/2 study, and designed to further evaluate the safety and efficacy of amsoki-cel at the recommended phase 2 dose (RP2D) in patients with ICI-resistant advanced melanoma....Enrollment is anticipated to be completed by end of Q1 2027....NSCLC Phase 1 data are expected in the first half of 2027."

Enrollment status • P1/2 data • Melanoma • Non Small Cell Lung Cancer

Obsidian Therapeutics to Present Phase 2 Clinical Data for OBX-115 in Advanced Melanoma in Oral Presentation at 2026 ASCO Annual Meeting (Yahoo Finance) - "73% of patients had progression after anti–PD-1 + anti–CTLA-4 doublet therapy. 67% ORR including 2 confirmed complete responses (CR) and 8 confirmed partial responses (PR). Durable clinical benefit, including 8 of 10 responses ongoing as of the median 4.3 month study follow-up. We have been in discussions with the FDA, and after reaching alignment on key design elements including eligibility criteria, clinical trial endpoints and drug product potency assay, plan to pursue a single-arm accelerated approval pathway. We look forward to continuing to advance OBX-115 through the clinic and plan to begin treating patients in the registration-enabling cohort of our multicenter study in mid-2026. Obsidian is also investigating OBX-115 in patients with non-small cell lung cancer (NSCLC) in the Agni-01 trial. NSCLC Phase 1 data are expected in the first half of 2027."

P1 data • P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer

Agni-01: Safety and Efficacy of OBX-115 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=208 | Recruiting | Sponsor: Obsidian Therapeutics, Inc. | Trial completion date: Jun 2028 ➔ Jun 2029 | Trial primary completion date: Jun 2028 ➔ Jun 2029

Trial completion date • Trial primary completion date • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • BRAF • PD-L1

OBX-115 membrane-bound IL15 (mbIL15)-expressing engineered tumor-infiltrating lymphocytes (TIL) overcome target cell immune evasion related to major histocompatibility complex (MHC) silencing through both direct killing and transactivation of NK cells in patient-derived autologous non-small cell lung cancer (NSCLC) models (AACR 2026) - "OBX-115 engineered TIL express mbIL15 under pharmacologic regulation using the FDA-approved small-molecule drug acetazolamide (ACZ). Our data demonstrate that, similar to previously reported MHC-I-independent tumoricidal effect observed in melanoma CD8+ T cells, OBX-115 engineered mbIL15-expressing NSCLC TIL partially retain cytotoxicity and reactivity toward autologous tumor cells in MHC-loss models. Further, transactivation of autologous NK cells via mbIL15 uniquely enhances activity."

Clinical • Late-breaking abstract • Tumor-infiltrating lymphocyte • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • B2M • CD8 • IFNG • IL15 • STAT5

Obsidian Therapeutics, Inc…announced an oral presentation of Phase 2 results in patients with advanced melanoma from the Phase 1/2 Agni-01 multicenter study of OBX-115, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in Chicago, IL, May 29–June 2, 2026. (National Law Review)

P2 data • Melanoma

Obsidian Therapeutics and Galera Therapeutics Announce Merger Agreement and $350 Million Concurrent Private Placement (Businesswire) - "In support of the transaction, Galera and Obsidian have secured commitments for an oversubscribed private placement financing that is expected to result in total gross proceeds of $350 million..The combined company’s cash and cash equivalents balance at closing, including the funds from the private placement financing, is anticipated to fund the combined company’s operations into the second half of 2028 and provides runway through key clinical milestones for Obsidian’s lead product candidate, OBX-115. These include Phase 1 data from the ongoing NSCLC trial expected in the first half of 2027, and by year-end 2027, topline data from their melanoma registration-enabling trial. The combined company will also continue to support Galera’s pipeline."

M&A • P1 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

Tumor-infiltrating lymphocytes (TIL) engineered with membrane-bound IL15 (cytoTIL15 cells) exhibit pharmacologically regulatable signal transduction in cis and trans (AACR 2024) - P1 | "The mbIL15 expressed by cytoTIL15 cells is regulated via a carbonic anhydrase 2 (CA2) drug-responsive domain, which allows expression to be induced upon delivery of the FDA-approved small molecule ligand acetazolamide (ACZ) and was designed to engage the IL2Rβ and IL2Rγ receptors in both cis and in trans. cytoTIL15 cells demonstrate functional engagement of cytokine receptors via mbIL15 in both cis and in trans, including phosphorylation of STAT5 and S6. Taken together, these data highlight the potential for robust activity of cytoTIL15 cells through potentiation of ACZ-dependent mbIL15 activity in both cis and trans."

Late-breaking abstract • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor • CD8 • IL15 • STAT5

OBX-115 TIL from non-small cell lung cancer (NSCLC) are enriched for putative tumor-reactive, stem-like T cells with enhanced tumor cytotoxicity: Results from multimodal phenotyping analysis (AACR 2025) - P1/2 | "Here, we demonstrate that the OBX-115 manufacturing process from NSCLC tumor tissue, incorporating cell-armored-mbIL15-driven expansion and 4-1BB agonism, generates higher TIL yield and a more stem-like phenotype than conventional non-engineered TIL process. Computational analysis reveals the OBX-115 process enriches for putative tumor-reactive TCR clonotypes, which is further supported by in vitro co-culture assays. Together, these favorable attributes support further investigation of OBX-115 in patients with metastatic NSCLC (NCT06060613)."

IO biomarker • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD69 • CD8 • ENTPD1 • IFNG • IL15 • IL2 • PD-1

Trial in progress: Phase 1/2 study of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced solid tumors (AACR 2025) - P1, P1/2 | "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...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...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."

Clinical • First-in-human • Metastases • P1/2 data • Tumor-infiltrating lymphocyte • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL15

Trial in progress: A phase 1/2 study to investigate the safety and efficacy of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma (AACR 2024) - P1, P1/2 | "OBX-115 TIL are engineered to express regulatable membrane-bound IL15 (mbIL15) under dose-dependent regulation using acetazolamide (ACZ), an FDA-approved small-molecule diuretic, avoiding the need for high-dose IL2...Cryopreserved OBX-115 is generated from the pt's own tumor tissue procured by surgical excision or core biopsy, and is infused after standard- or low-dose (based on clinical eligibility) lymphodepletion (cyclophosphamide and fludarabine)...No systemic high-dose IL2 is administered. Two sites are open and recruiting pts."

Checkpoint inhibition • Clinical • First-in-human • Metastases • P1/2 data • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor • IL15

OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy induced deepening and durable responses without interleukin 2 (IL2) in patients (pts) with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma (AACR 2024) - P1, P1/2 | "OBX-115 is an investigational, autologous TIL cell therapy engineered to express membrane-bound IL15 (mbIL15) under pharmacologic regulation by the FDA-approved small-molecule drug acetazolamide (ACZ) using cytoDRiVE® technology, to induce cytokine-driven TIL expansion and persistence without co-administration of IL2. This Phase 1 first-in-human study (NCT05470283) is assessing the safety, tolerability, and efficacy of the OBX-115 regimen in pts with unresectable or metastatic melanoma progressing after ICI...OBX-115 is manufactured using the pt's tumor tissue (procured by surgical excision or core needle biopsy) and infused after completion of cyclophosphamide and fludarabine lymphodepletion... OBX-115, a one-time, IL2-free, regulatable, engineered TIL cell therapy, was well-tolerated and induced consistently deepening and durable responses, with the potential to fulfill the unmet need in ICI-resistant advanced melanoma. These early results support..."

Checkpoint inhibition • Clinical • First-in-human • Metastases • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor • IL15 • IL2

Tumor-infiltrating lymphocytes (TIL) engineered with regulatable membrane-bound IL15 (mbIL15) and LIGHT (TNFSF14) show enhanced efficacy in fibroblast-containing cold tumors (AACR 2024) - P1 | "We have developed OBX-115, TIL engineered to express mbIL15 regulatable using the cytoDRiVE® platform, which allows for TIL expansion, persistence, and anti-tumor efficacy under control of the FDA-approved small-molecule ligand, acetazolamide (ACZ), eliminating the need for co-administration of IL2 (NCT05470283). These preclinical results suggest that TIL engineered with regulatable mbIL15 and LIGHT using the cytoDRiVE platform have the potential to address the high unmet clinical need in cold tumors with suppressive TME, which are currently not amenable to ACT."

Clinical • IO biomarker • Late-breaking abstract • Tumor-infiltrating lymphocyte • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL15 • IL2 • TNFA • TNFSF14

Evolving therapeutic pipeline for tumor-infiltrating lymphocytes in metastatic melanoma - a review. (PubMed, Front Immunol) - "The recent U.S. FDA approval of lifileucel, a non-engineered, autologous tumor-infiltrating lymphocyte (TIL) therapy, for unresectable or metastatic melanoma represents a major milestone for cellular therapies in solid tumors...OBX-115, designed with regulatable membrane-bound IL-15 expression, eliminates the need for IL-2 infusion and has shown early clinical activity. KSQ-001EX uses CRISPR/Cas9 to inactivate SOCS1, while KSQ-004EX additionally targets Regnase-1 to enhance TIL function...TIL therapy remains among the most promising strategies in melanoma and solid tumors after immunotherapy failure. Ongoing research aims to optimize cell dose, phenotype, tumor procurement, treatment sequencing, and rational combinations to improve durable benefit."

IO biomarker • Journal • Review • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor • IL15 • SOCS1

Agni-01: Safety and Efficacy of OBX-115 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=208 | Recruiting | Sponsor: Obsidian Therapeutics, Inc. | N=52 ➔ 208

Enrollment change • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • BRAF • PD-L1

Translational data validate OBX-115 mechanism of action: impact of dosing on clinical outcome in advanced melanoma (SITC-SSC 2026) - No abstract available

Clinical • Clinical data • Metastases • Melanoma • Solid Tumor

Potent cytotoxic tumor-infiltrating lymphocytes can be generated from immune-excluded chondrosarcomas using regulatable membrane-bound IL15. (PubMed, Cancer Immunol Res) - "Here, we report the successful generation and expansion of TIL engineered with regulatable, membrane-bound IL15 (cytoTIL15™ cells) from immune-excluded, paucicellular chondrosarcoma biopsies largely consisting of collagenous matrix and demonstrate that these cells have potent tumor-killing capacity in cell culture and in tumor spheroid models in the absence of exogenous IL2...Moreover, we demonstrate that IL15 reduced the signaling threshold of T-cell receptors isolated from TIL clonotypes, increasing their infiltration and cytotoxicity in autologous 3D tumor models. These results suggest the possibility of developing an effective IL2-free TIL therapy for patients with immune-excluded tumors."

IO biomarker • Journal • Tumor mutational burden • Tumor-infiltrating lymphocyte • Cervical Cancer • Kidney Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • IL15 • IL2 • TMB

Novel tumor-infiltrating lymphocytes therapy in solid tumors: latest updates from 2025 ASCO annual meeting. (PubMed, Exp Hematol Oncol) - "Notably, innovative TIL-based monotherapies and combination regimens have provided durable clinical responses and survival benefits for patients with various solid tumors. This article summarizes recent advances in TIL therapy for solid tumors presented at the 2025 ASCO Annual Meeting, highlighting monotherapies such as Lifileucel, LM103, OBX-115, GT101, GT300, GT201, and HS-IT101, as well as combination strategies with the oncolytic adenovirus TILT-123 or pembrolizumab."

Journal • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor

Translational data validate OBX-115 mechanism of action: Impact of dosing on clinical outcome in advanced (adv) melanoma (ESMO 2025) - P1/2 | "Background OBX-115 TIL express membrane-bound IL15 (mbIL15) regulated by the FDA-approved small-molecule drug acetazolamide (ACZ), abrogating the need for IL2 and resulting in differentiated safety and promising efficacy (Amaria ASCO 2024, Chesney ASCO 2025). This regimen allows for low-dose LD and no IL2, which may expand pt eligibility. Ph 2 enrollment is ongoing."

Clinical • Clinical data • Metastases • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • IL15 • IL2 • NCAM1