By Dr. Sajeve Thomas, Board-Certified Medical Oncologist | AdventHealth Cancer Institute
There are moments in oncology when data lands and you think: this changes the conversation.
For me, the presentation of OBX-115 at the 2026 ASCO Annual Meeting was one of those moments.
I have been following the work of Obsidian Therapeutics for some time now, and I am proud to share that one of the very first clinical trials we are opening at AdventHealth Cancer Institute is the Agni-01 study — the trial evaluating OBX-115 in patients with advanced melanoma who have progressed on immunotherapy. We are currently working through regulatory processes and expect to be enrolling patients in the coming months. I recently returned from an investigator meeting in Nashville with the Obsidian team and co-investigators from across the country, and I left genuinely excited about what this therapy may mean for our patients.
Let me walk you through what the data shows — and why I think it matters.
What Is OBX-115, and Why Is It Different?
You may have heard of TIL therapy — tumor-infiltrating lymphocyte therapy. The basic idea is that your own immune cells, which have already entered your tumor, are harvested, expanded in the lab, and re-infused in large numbers to fight your cancer. The FDA-approved TIL therapy lifileucel (Amtagvi) has already shown meaningful responses in melanoma, and I have written about this approach before.
OBX-115 is a next-generation, engineered TIL therapy. And the engineering is what makes this different.
The cells are modified to express a regulatable membrane-bound form of interleukin-15 (mbIL15). IL-15 is a cytokine — a chemical messenger — that helps T cells survive, expand, and stay active. Here is the clever part: the IL-15 is kept in an “off” state inside the cell until the patient takes acetazolamide (ACZ), an oral pill. When the patient takes ACZ, it stabilizes a molecular switch, turning IL-15 “on.” This allows physicians to control — and reinduces — T-cell expansion over time just by giving the patient a pill.
This approach has three major implications for patients:
No high-dose IL-2. Conventional TIL therapy typically requires interleukin-2 infusions to support T-cell survival after infusion. IL-2 at high doses is notoriously toxic — it can cause capillary leak syndrome, hypotension, and requires intensive inpatient monitoring. OBX-115 eliminates this entirely. The IL-15 does the job, driven by an oral drug the patient can take at home.
Low-dose lymphodepletion — potentially as an outpatient. To make room for the new T cells, patients typically require chemotherapy to “deplete” the immune system first (lymphodepletion). With OBX-115, the lymphodepletion regimen is lower intensity — and in some cases has been administered in the outpatient setting.
Tissue procurement by core needle biopsy. Most TIL therapies have required surgical procedures to harvest enough tumor tissue. OBX-115’s manufacturing process is designed to work with minimally invasive core needle biopsies in many cases, which significantly reduces procedural burden for patients.
Together, these features are designed to make engineered TIL therapy accessible to patients who might otherwise not qualify or tolerate standard TIL approaches.
What Did the Data Show at ASCO 2026?
The Agni-01 trial (NCT06060613) is a Phase 1/2 multicenter study. Dr. Allison Betof from Stanford University School of Medicine presented updated results from 15 patients treated at the recommended Phase 2 dose.
This was a genuinely difficult patient population. The median number of prior lines of therapy was 2. Nearly all patients (93%) had received prior anti-PD-1 combination therapy — 73% had received ipilimumab plus nivolumab. Nearly three-quarters were primary-resistant to immune checkpoint therapy. The group also included patients with mucosal melanoma (20%) and acral melanoma (20%), subtypes that historically respond poorly and have limited options.
Despite all of that, here is what OBX-115 produced:
- Objective response rate: 67% (10 out of 15 patients)
- Complete responses: 13% (2 patients)
- Partial responses: 53% (8 patients)
- Disease control rate: 93%
- Median duration of response: not yet reached (range 1.1+ to 14.9+ months)
Most responses were achieved early — by week 6. Importantly, responses were observed across the full range of difficult-to-treat subtypes: BRAF-mutant disease, ICI primary-resistant patients, and patients previously treated with combination checkpoint therapy.
One case that stood out to me: a 44-year-old patient with stage IV mucosal melanoma involving the liver, who had progressed on ipilimumab/nivolumab and was primary-resistant. After OBX-115, they achieved a 41% reduction in their liver metastasis by week 6 — and at week 36, the response had deepened further to a 60% reduction, and was still ongoing.
That pattern — responses deepening over time — appeared consistently across the swimmer’s plot. The biology of ACZ-driven IL-15 reactivation may be contributing to this continued tumor control.
Is It Safe?
This is where OBX-115 stands out even further.
- No dose-limiting toxicities
- No ICANS (immune effector cell-associated neurotoxicity syndrome)
- No ICU transfers
- No treatment-related deaths
- Cytokine release syndrome occurred in 5 patients (33%), but only 1 case (7%) was Grade 3
- IL-6 levels remained well below the classical CRS range — tocilizumab was not needed
- Most treatment-related adverse events were Grade 1 or 2 and occurred in the first two weeks after infusion
ACZ redosing — the oral pill patients take to reactivate their T cells — was well tolerated in the outpatient setting across all patients who received it.
The safety profile here is not just reassuring. It is a genuine differentiator that could expand who can be offered cell therapy.
Who Might This Apply To?
Based on what is currently being studied in the Agni-01 protocol, OBX-115 is being evaluated in:
- Second-line advanced melanoma — patients whose disease has progressed on or after immune checkpoint therapy (the setting presented at ASCO)
- Second-line non-small cell lung cancer — a new and expanding cohort
- First-line metastatic melanoma — for patients who are treatment-naive or who have received only one to two doses of pembrolizumab
This is significant. Bringing an engineered TIL approach into the first-line setting, or into lung cancer, would represent a major expansion of what cell therapy can offer.
What This Means for Our Patients
For my patients here in Central Florida, this trial matters.
After immunotherapy stops working in melanoma, the road narrows quickly. Patients with BRAF-mutant disease may have targeted therapy options. Some patients are candidates for lifileucel. But for many — particularly those who are older, have marginal performance status, or cannot tolerate intensive inpatient admissions — conventional TIL therapy has not been a realistic option.
OBX-115 is designed to change that calculus. Outpatient lymphodepletion. No IL-2. Core needle biopsy. An orally regulatable cytokine support system. And 67% response rates in patients who have already failed combination immunotherapy.
That is not a minor step forward.
We are working hard to get this trial open at AdventHealth Cancer Institute, and I anticipate we will be enrolling patients in the months ahead. If you or someone you love has advanced melanoma, non-small cell lung cancer, or another cancer type that may become eligible in future cohorts — please reach out. Early awareness means you can plan ahead, not react under pressure.
As always, the conversation starts here.
Disclosure: Dr. Thomas is an investigator on the Agni-01 trial. Any patient scenarios referenced are fictionalized educational illustrations and do not represent specific individuals. The views expressed are Dr. Thomas’s own and do not represent AdventHealth. This post is intended for general educational purposes and does not constitute medical advice. Please speak with your treating physician about your specific situation.
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