Melanoma cell therapy controlled by an approved drug enrolls new groups

An experimental cancer treatment that is built from a patient’s own immune cells, then switched on with an ordinary approved drug, is now recruiting new groups of people with advanced melanoma, the most dangerous form of skin cancer. The therapy, called OBX-115 and made by Obsidian Therapeutics, is being tested in a trial with about 254 people planned.¹ Its first melanoma group has finished enrolling, while new melanoma groups, including one for people earlier in their treatment, are now taking patients.²

This is Biohack’s first article on this therapy. It sets out what the trial is testing, what has been reported so far, and what is still unknown.

How the treatment works

OBX-115 belongs to a family of treatments called TIL therapy, short for tumor-infiltrating lymphocytes. These are immune cells that have already found their way into a tumor. The approach is to collect them, grow many more in a lab and give them back to the patient.

For OBX-115, doctors take a patient’s own T cells, a type of white blood cell, from tumor tissue and genetically modify them to target the cancer cells.² The added piece is a version of IL-15, a natural signal that helps immune cells grow and survive, attached to the surface of the cell.³ That signal is controlled with acetazolamide, a drug approved by the US Food and Drug Administration (FDA) as a mild diuretic.² In the trial, acetazolamide is given for a short time to “activate” the cells so they attack the cancer.²

The control system comes from what Obsidian calls its cytoDRiVE technology, which it says lets FDA-approved small-molecule drugs set when, and how strongly, a protein works.³ Older, unmodified TIL therapy depends on IL-2, another immune signal given as a drug.³ The researchers running the trial say they believe the combination may cause less severe side effects and work better than other T cell therapies, but that remains a belief being tested.²

Who the trial is for

The study is a Phase 1/2 trial, an early test that first looks for a safe dose and then begins to check whether the treatment shrinks tumors. It is open-label, meaning doctors and patients know who is getting the therapy, and there is no comparison group. It began on October 25, 2023, and is listed as recruiting.¹

Participants must be adults with advanced melanoma that cannot be removed by surgery or has spread, or with a type of lung cancer called non-small cell lung cancer that has come back or stopped responding to treatment.² The study is divided into groups:

• Group 1 (enrollment complete): people with melanoma whose cancer grew after a PD-1 or PD-L1 drug, the immune checkpoint medicines that are a standard melanoma treatment, and who have had no more than two earlier lines of treatment.²
• Group 2 (recruiting): people with non-small cell lung cancer that relapsed or did not respond to approved treatments.²
• Group 3 (recruiting): another melanoma group with similar rules to Group 1. People whose tumors carry a BRAF mutation do not need to have taken BRAF-blocking drugs first.²
• Group 4 (recruiting): people at the start of treatment for advanced melanoma, who may have had up to two doses of a PD-1 or PD-L1 drug but must not have known cancer growth before their tumor sample is collected.²

Patients must also be in good enough health to carry out daily activities, have a life expectancy of more than six months, and have at least one tumor that can be measured after tissue is taken to make the cells.² The goal is to find the recommended dose of OBX-115 with acetazolamide, and to study safety, how well it treats the cancer, and how well patients tolerate it.²

The evidence so far

The only results described in the sources reviewed for this article come from the company. Obsidian presented early Phase 1 data at the 2024 American Society of Clinical Oncology (ASCO) annual meeting, a major cancer conference.³ According to a summary of those data, the therapy showed a favorable safety profile compared with unmodified TIL therapy that depends on IL-2, and what was described as promising efficacy in patients who had already had many treatments.³ The company also reported that the cells could be made from tumor tissue collected with a core needle biopsy, a thin needle, rather than requiring surgery.³

A company publication from April 2024 is titled as reporting “deepening and durable responses” without IL-2 in melanoma patients whose cancer had resisted checkpoint drugs.⁴ The text of that page available to Biohack did not include patient numbers, response rates or side effect figures, so this article does not report any.

What it does not show yet

Early company data like these can point to whether a treatment is worth testing further. They cannot show that it helps people live longer, or that it does better than existing options. The trial has no comparison group, and the reported figures have not been posted to the public trial registry: as of the registry record, no results had been posted.¹

The trial’s two main measures are the rate of serious side effects that limit the dose, tracked over the first 28 days, and the share of patients whose tumors shrink partly or fully on scans, tracked over two years.¹ Its primary completion date, when the main data are expected to be collected, is listed as June 30, 2029.¹ Questions about how long any responses last, and how the newer groups fare, remain open until then.

Who is behind it

Obsidian Therapeutics, based in Cambridge, Massachusetts, sponsors the trial.¹ The company develops engineered cell and gene therapies and has collaborations with the drugmakers Bristol Myers Squibb and Vertex Pharmaceuticals.³ OBX-115 is the lead product in its cytoTIL15 program, which the company says aims to improve how long TIL cells last in the body, how well they fight tumors, and how safe they are.³

Because Obsidian makes the therapy and paid for the trial, the early results described so far reflect its own presentation of the data. Parameswaran Hari, the company’s chief development officer, said the FDA’s recognition underscored the need for new treatments when melanoma resists checkpoint drugs.³

What regulators have said

In July 2024 the FDA gave OBX-115 Fast Track designation, and in September 2024 it added Regenerative Medicine Advanced Therapy (RMAT) designation for melanoma that does not respond to checkpoint drugs.³ RMAT was created under the 21st Century Cures Act. To qualify, a cell therapy must target a serious or life-threatening condition and show early clinical evidence that it could meet an unmet need.³ The designation brings early and frequent meetings with the FDA and opens the possibility of accelerated approval and priority review.³ Neither designation is an approval, and neither means the FDA has judged the treatment effective.

What to watch next

• Results from the newer melanoma groups, especially Group 4, which tests the therapy earlier in treatment.²
• Data from the lung cancer group, which would show whether the approach carries beyond melanoma.²
• Full results with patient numbers, response rates and side effects, ideally reviewed by outside scientists, and results posted to the public registry.¹
• Any further steps with the FDA, which the company has said it will keep working with on melanoma and lung cancer.³

Biohack will update this thread when new, verifiable results appear.