FDA Grants RMAT Designation to Novel TIL Therapy OBX-115 in Melanoma
This designation follows the fast track designation that was granted to OBX-115 for the same indication in July 2024.
Tumor infiltrating lymphocytes and oncolytic adenovirus for patients with metastatic malignant melanoma
- The FDA has granted a regenerative medicine advanced therapy (RMAT) designation to OBX-115 for the treatment of patients with unresectable or metastatic melanoma that has been resistant to immune checkpoint inhibitor (ICI) therapy.
- OBX-115 is a novel tumor-infiltrating lymphocyte (TIL) therapy.
- In July 2024, the FDA granted the agent fast track designation.
OBX-115, a novel TIL therapy, has been granted FDA RMAT designation in unresectable or metastatic melanoma resistant to ICI therapy.1
RMAT can be granted to agents that intend to treat, modify, reverse, or cure serious or life-threatening conditions and have preliminary evidence that demonstrate the agent’s potential to address serious unmet needs in these conditions.2
In July 2024, the FDA also granted OBX-115 fast track designation for the same indication.1
Compared with other TIL therapies, OBX-115 is engineered and does not require the use of interleukin-2, which offers an improved safety profile.
Rodabe Amaria, MD
“OBX-115 is a clear step forward, because the cells are engineered, and we don't have to use an exogenous cytokine. I really think that we're at an exciting area in the space of TIL therapy,” said Rodabe Amaria, MD, medical oncologist in the Department of Melanoma Medical Oncology, Division of Cancer Medicines, at MD Anderson Cancer Center, in an interview with Targeted OncologyTM. “The important thing is moving the science forward [by] working on engineering and novel ways to make these T cells better and also safer for our patients.”
OBX-115 is being investigated in a phase 1 study (NCT05470283), and findings were presented at the 2024 American Society of Clinical Oncology Annual Meeting. In patients with unresectable or metastatic melanoma resistant to ICI (n = 9), the combination of OBX-115 and acetazolamide had an objective response rate (ORR) of 44.4%. This included complete response and partial response rates of 22.2% each.Among those given 30 billion cells at OBX-115 infusion (n = 6), the ORR was 50%.3
A total of 55.6% of patients had stable disease that lasted for at least 12 weeks. No patients had progressive disease, which translated to a disease control rate of 100%. At 24 weeks, the progression-free survival (PFS) rate was 75%.
In this open-label, first-in-human trial, investigators are enrolling patients with advanced melanoma that is relapsed and/or refractory to ICIs. Enrollment is open to patients with an ECOG performance status of 0 to 1, at least 1 lesion for tumor tissue procurement for the manufacturing of OBX-115, and 1 or more remaining lesion to assess response per RECIST 1.1 criteria. Patients with mucosal melanoma, uveal melanoma, and other high-risk diseases were eligible for enrollment following the establishment of OBX-115’s initial safety. The same applied to patients with genomically equivalent mutations.4
The study’s primary end points are safety/tolerability and establishing the recommended doses of OBX-115. Secondary end points include ORR, duration of response, and PFS.
Regarding safety, at a median follow-up of 29.5 weeks (range, 13.0-69.3), there was no treatment- or disease-related mortality reported. None of the patients required admission to an intensive care unit, there were no dose-limiting toxicities reported, and there were no cases of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or capillary leak syndrome.3
Seven patients given redosing, outpatient acetazolamide at week 6 did not experience any adverse effects (AEs). AEs also did not result in any treatment discontinuation. There were no grade 4 or higher nonhematologic treatment-emergent AEs (TEAEs) observed among those in the study. Among all evaluable patients (n = 10), nonhematologic TEAEs seen consisted of increased alanine aminotransferase (any grade, 40%; grade 3, 10%), abdominal pain (10%; 10%), and syncope (10%; 10%).
Hematologic AEs were consistent with the known safety profile of lymphodepletion. Grade 1/2 rash or pruritus was reported in 8 patients. Four patients experienced grade 1/2 uveitis/iritis, and 1 of these patients had grade 3 optic neuritis, which later resolved.
“RMAT designation for OBX-115 highlights the unmet need in ICI-resistant melanoma and OBX-115’s potential to provide patient-centric, transformative care in this setting,” said Parameswaran Hari, MD, Chief development officer of Obsidian Therapeutics, in a press release.1
