Obsidian Therapeutics Reports Promising Amsoki-Cel Results in ICI-Resistant Advanced Melanoma, With 67% Response Rate
Obsidian Therapeutics, a clinical-stage biopharmaceutical company developing engineered tumor-infiltrating lymphocyte (TIL) cell therapies through its proprietary protein-regulation technology, has announced positive updated clinical results for amsokigene autoleucel (amsoki-cel, formerly known as OBX-115). The findings come from patients with immune-checkpoint inhibitor (ICI)-resistant advanced melanoma enrolled in the company’s Phase 1 first-in-human (FIH) study and Phase 1/2 Agni-01 multicenter clinical study.
The updated results will be presented in a poster session on Saturday, November 7, 2026, at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting in Phoenix, Arizona. The findings highlight the investigational cell therapy’s clinical activity, durability of responses and safety profile in a patient population with advanced melanoma that has progressed following immune-checkpoint inhibitor treatment.
Amsoki-cel is an engineered TIL cell therapy designed to address some of the treatment-related challenges associated with conventional TIL approaches. The therapy incorporates pharmacologically regulatable membrane-bound interleukin-15 (IL-15), a feature intended to support the activity of engineered T cells while allowing their function to be regulated through a pharmacological mechanism.
The treatment is also being developed with a patient-centric approach intended to reduce the burden associated with receiving TIL therapy. Its proposed treatment regimen includes the option to obtain tumor tissue through a less-invasive core needle biopsy (CNB), exclusively low-dose lymphodepletion (LD) that may be compatible with outpatient administration, and elimination of interleukin-2 (IL-2) from the treatment regimen.
These features are intended to simplify several aspects of the treatment process while preserving the potential clinical benefits of TIL-based immunotherapy. The updated clinical findings provide additional information about the therapy’s performance in patients whose melanoma has continued to progress despite previous immune-checkpoint inhibitor treatment.
Updated Efficacy Results from the Agni-01 Multicenter Study
The updated efficacy findings are based on the single-arm, open-label Phase 1/2 Agni-01 study (NCT06060613). The multicenter clinical trial is evaluating the safety and efficacy of amsoki-cel in adults with advanced melanoma that has progressed following treatment with immune-checkpoint inhibitors.
The efficacy analysis presented at SITC 2026 includes 15 patients treated at the recommended Phase 2 dose (RP2D). The data cutoff for this updated analysis was September 25, 2026.
The patient population represents a group with substantial unmet medical needs. Most participants had previously received combination immune-checkpoint inhibitor therapy, including treatment with anti-PD-1 and anti-CTLA-4 agents. Specifically, 93% of patients had received doublet ICI treatment, while 73% had experienced disease progression following anti-PD-1 plus anti-CTLA-4 combination therapy.
This treatment history is important because patients whose melanoma progresses after combination checkpoint inhibition often have limited treatment options. The updated results therefore provide information about the potential role of engineered TIL therapy in patients who have already received established immunotherapy approaches.
Among the 15 patients treated at the RP2D, amsoki-cel achieved an objective response rate (ORR) of 67%, based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The responses included two confirmed complete responses (CRs) and eight confirmed partial responses (PRs).
The findings indicate that a substantial proportion of patients experienced measurable tumor responses following treatment. Complete responses represent the disappearance of detectable target lesions under the applicable response criteria, while partial responses indicate a significant reduction in tumor burden.
In addition to the overall response rate, the company reported evidence of sustained clinical benefit. At a median follow-up of 14.3 months, five of the ten responses remained ongoing. This suggests that responses observed with amsoki-cel may persist beyond the initial period following infusion in some patients.
Responses Continued to Deepen During Follow-Up
The updated analysis also includes additional observations that became available after the May 5, 2026, data cutoff used for the earlier abstract and pooled safety analysis.
Since that earlier cutoff, one patient’s partial response deepened to a 100% reduction in the sum of diameters (SOD) of target lesions at six months after infusion. This brought the total number of patients with a 100% reduction in target-lesion measurements to two, alongside two patients who achieved confirmed complete responses.
All four of these responses remained ongoing at the time of the updated analysis.
The company also reported encouraging findings at the 12-month post-infusion landmark. At that time point, 33% of all patients treated at the recommended Phase 2 dose, or five of the 15 participants, remained in deep, ongoing response.
Among these five patients, reductions in the sum of diameters of target lesions ranged from 72% to 100%. Four patients had achieved a 100% reduction, while one patient had a 72% reduction. All five responses were ongoing at the reported assessment.
The continued deepening of responses over time is a notable aspect of the updated findings. It indicates that some patients may experience further reductions in measurable tumor burden following the initial response assessment.
For patients with advanced melanoma that has progressed after multiple immune-checkpoint inhibitor treatments, the durability of a response is an important consideration. While the results remain based on a relatively small clinical study population, the persistence of responses at the one-year landmark provides additional evidence supporting continued evaluation of amsoki-cel.
Progression-Free Survival and Duration of Response
The updated Agni-01 efficacy analysis also reported a median progression-free survival (mPFS) of 8.3 months. Progression-free survival measures the time patients remain alive without their disease worsening after treatment.
Median duration of response (mDOR) had not been reached at the reported median study follow-up of 14.3 months. This means that the available follow-up data were not yet sufficient to determine the time point at which half of the responding patients would have experienced disease progression or another event ending their response.
The fact that median duration of response had not been reached, together with the ongoing responses observed at the 12-month landmark, provides further information about the potential durability of amsoki-cel treatment.
However, the findings are still from an early-stage, single-arm study involving 15 patients treated at the recommended Phase 2 dose. Additional clinical data and longer follow-up will be needed to better characterize the treatment’s efficacy, durability and potential role in the management of ICI-resistant advanced melanoma.
Pooled Safety Data Show a Consistent Profile
Alongside the updated efficacy results, Obsidian will present pooled safety findings from 37 patients enrolled in the Phase 1 FIH single-center study (NCT05470283) and the Phase 1/2 Agni-01 multicenter study (NCT06060613).
The pooled safety analysis uses a May 5, 2026, data cutoff and provides a broader assessment of the therapy’s tolerability across the two clinical studies.
According to the company, amsoki-cel demonstrated a consistent and favorable safety profile across the pooled patient population. No dose-limiting toxicities (DLTs), treatment-related mortality (TRM), immune effector cell-associated neurotoxicity syndrome (ICANS) or intensive care unit (ICU) transfers were reported.
The company also reported that the majority of non-hematologic treatment-emergent adverse events (TEAEs) occurring in at least 30% of patients were Grade 2 or lower. One Grade 3 cytokine release syndrome (CRS) event was reported.
These safety findings are relevant to the continued development of engineered TIL therapies. Cell-based immunotherapies can involve treatment-related toxicities that require close monitoring and specialized clinical management. The absence of reported treatment-related mortality, ICANS, dose-limiting toxicities and ICU transfers in the pooled population provides additional information about the safety profile observed to date.
Nevertheless, the safety results should be interpreted in the context of the study size and the early stage of clinical development. Larger patient populations and additional follow-up will be necessary to establish a more comprehensive understanding of potential adverse events and treatment risks.
Core Needle Biopsy Could Offer a Less-Invasive Tissue Collection Option
The pooled analysis also provides information about how tumor tissue was obtained for manufacturing the personalized TIL cell therapy.
Among the 37 patients included in the safety population, 10 patients, representing 27%, had tumor tissue acquired through core needle biopsy. The remaining 27 patients, or 73%, underwent surgical resection for tissue procurement.
The use of CNB is an important component of Obsidian’s patient-centric development strategy. Conventional TIL treatment approaches generally require the collection of tumor tissue through a surgical procedure. A less-invasive biopsy option could potentially reduce the procedural burden for eligible patients and expand the range of circumstances in which tumor tissue can be collected.
The ability to use CNB may also be relevant for patients with advanced disease who could face additional challenges associated with more invasive tissue collection procedures. The reported experience in 10 patients demonstrates that CNB was used as a tissue procurement method within the clinical program.
Obsidian’s broader approach combines this option with low-dose lymphodepletion and the elimination of IL-2 from the treatment regimen. Together, these elements are intended to make the treatment process more manageable for patients and potentially support administration in outpatient settings.
Clinical Experts Highlight Potential Patient Benefits
Rodabe Amaria, M.D., professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center and the lead author and presenter of the SITC poster, highlighted the potential significance of the updated findings.
According to Dr. Amaria, the combination of promising efficacy, response durability and safety in patients with ICI-resistant advanced melanoma supports further evaluation of amsoki-cel as a potential treatment option.
She also emphasized the importance of the therapy’s treatment approach. The option of minimally invasive core needle biopsy for tumor tissue procurement, low-dose lymphodepletion compatible with outpatient administration and the absence of IL-2 in the regimen could help reduce some of the burdens associated with TIL therapy.
Dr. Amaria noted that these treatment features may contribute to improving the accessibility of TIL-based approaches while maintaining the potential to deliver durable clinical benefit.
Parameswaran Hari, M.D., M.S., chief medical officer of Obsidian Therapeutics, also commented on the updated results. He highlighted the median progression-free survival of 8.3 months and the fact that median duration of response had not been reached at a median follow-up of 14.3 months.
Dr. Hari said the company was particularly encouraged by the durability of responses, including the finding that 33% of patients treated at the recommended Phase 2 dose continued to demonstrate ongoing responses at the one-year landmark.
He also pointed to the continued deepening of responses over time as an important observation from the updated analysis.
Registration-Enabling Cohort Enrollment Continues
Obsidian reported that enrollment in the registration-enabling cohort of its multicenter study is ongoing. The company expects enrollment to be completed by the end of the first quarter of 2027.
The company plans to report topline data from this cohort by the end of 2027. These upcoming results are expected to provide further information as the clinical program advances toward a potential registration pathway.
The registration-enabling cohort represents an important next step in the development of amsoki-cel. Additional clinical evidence will be needed to determine whether the encouraging response rate, durability and safety observations reported to date can be confirmed in a larger patient population.
Results Published in Nature Medicine
In addition to the SITC presentation, Obsidian announced that results summarizing safety and efficacy data from the FIH and ongoing Agni-01 studies were published in Nature Medicine on November 3, 2026.
The publication is titled “Regulatable Membrane-Bound IL-15 Engineered TIL Cell Therapy for Immune Checkpoint Inhibitor-Resistant Advanced Melanoma: Pooled Analysis of Phase 1 and 1/2 Trials.”
The publication includes data using the May 5, 2026, cutoff and provides a peer-reviewed account of the clinical experience with the investigational engineered TIL therapy across the two studies.
The article is available through the journal’s website, while the SITC 2026 poster can be accessed through the Publications section of Obsidian Therapeutics’ website.
Amsoki-Cel Development Also Expands into Non-Small Cell Lung Cancer
Beyond advanced melanoma, Obsidian is evaluating amsoki-cel in patients with non-small cell lung cancer (NSCLC) as part of the Agni-01 clinical program.
The company expects to report Phase 1 data from the NSCLC evaluation in the first half of 2027. This expansion reflects Obsidian’s interest in investigating whether its engineered TIL platform may have potential applications in additional solid tumors.
NSCLC is a broad category of lung cancer, and the planned clinical evaluation will provide early information about the therapy’s safety and potential activity in this separate patient population.
Overall, the updated melanoma findings provide additional clinical evidence for amsoki-cel, including a 67% objective response rate among patients treated at the recommended Phase 2 dose, ongoing responses in one-third of patients at the 12-month landmark, and a median progression-free survival of 8.3 months. The pooled safety findings and use of core needle biopsy for tumor tissue collection also offer insight into the company’s efforts to develop a potentially less burdensome TIL treatment approach.
As Obsidian continues enrollment in its registration-enabling cohort and advances the NSCLC evaluation, further clinical results will be important in determining the therapy’s long-term potential across patients with advanced solid tumors.
About Amsokigene Autoleucel (amsoki-cel, formerly OBX-115)
Obsidian leverages its cytoDRiVE® platform to develop engineered TIL cell therapies. Obsidian’s lead investigational TIL program, amsoki-cel, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15).
Amsoki-cel has the potential, if approved, to become a meaningful therapeutic option for patients with advanced (unresectable or metastatic) melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process designed to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. Obsidian is investigating amsoki-cel in the Phase 1/2 Agni-01 multicenter trial in patients with advanced solid tumors (NCT06060613).
About Obsidian Therapeutics
Obsidian Therapeutics, Inc. is a clinical-stage biopharmaceutical company harnessing novel protein-regulation technology to develop engineered TIL cell therapies for the treatment of patients with solid tumors. Obsidian’s proprietary cytoDRiVE® technology is designed to precisely regulate the timing and level of protein function by using FDA-approved small-molecule drugs. Obsidian has offices in Cambridge and Bedford, MA.