OBX-115: A Promising TIL Therapy for Melanoma

OBX-115 is a novel engineered tumor infiltrating lymphocyte (TIL) therapy designed to treat patients with checkpoint inhibitor-resistant metastatic melanoma. Unlike traditional TIL therapies that require toxic high-dose interleukin-2 (IL2), OBX-115 incorporates a regulated IL15 system, eliminating the need for this harmful cytokine.

Early results from a phase 1 study (NCT05470283) are encouraging. OBX-115 was well-tolerated with no severe adverse effects. Importantly, it demonstrated significant antitumor activity, leading to durable responses in half of the patients studied. This includes 2 complete remissions and 1 partial remission. The therapy also showed no sign of promoting brain metastases, a common concern with cancer treatments.

These findings suggest that OBX-115 has the potential to be a safe and effective treatment option for patients with advanced melanoma who have failed other therapies. Further studies are ongoing to confirm these promising results.

Here, Rodabe Amaria, MD, medical oncologist in the Department of Melanoma Medical Oncology, Division of Cancer Medicines, at MD Anderson Cancer Center, discusses the background and findings of this study.

Transcription:

0:05 | We are using in the study a novel T-cell therapy called OBX-115. So a little bit of background here: TIL is basically stands for tumor infiltrating lymphocytes. The idea is we take a patient with metastatic melanoma, subject them to some kind of surgery to remove a piece of melanoma tissue, that tissue gets sent to a lab. From there, we grow lots and lots of T cells that can be engineered to be really active, antimelanoma, little fighters. And then we infuse them back into the patient after giving them a course of chemotherapy. Traditionally, we use a medication called high-dose IL2 after the T cells are infused to make an environment where the T cells can grow and thrive. But that's really associated with toxicity. And what we're doing with OBX-115 is totally changing the way that we're doing TIL. We still have the component of taking tumor out; we still grow them in a lab. But our lab has the technique to basically genetically manipulate these T cells to make them better and to prevent them from having to use IL2. So basically, we can turn those T cells on after we infuse them into the patient, we can give an FDA-approved small molecule inhibitor, turn the T cells on, and when we turn those T cells on, it makes its own cytokines. So instead of having to use IL2, we can regulate the expression of the cytokine. And in that way, we think it's safer, we think we can offer this to a bigger pool of patients. And we think the T cells are just better overall.
1:44 | This is a first-in-human study, and we're really only presenting data on the first 10 patients, specifically 9 patients included in the per protocol efficacy analysis. And here we found a response rate of 44%, including 22% of patients having a complete response. Additionally, there were no patients with primary progressive disease. So 100% disease control rate. 75% of the patients were progression-free at 24 weeks. And because this was a dose escalation, if we specifically look at the group of patients that received over 30 billion TIL, response rate is 50%. Additionally, we did a lot of analysis on safety. We really didn't see any unexpected safety profiles. We saw expected side effects from the chemotherapy. And otherwise we saw a low-level rash, right, as from the actual T cell infusion.