IMA203, a T-cell receptor therapeutic agent targeting PRAME, showed positive activity in a variety of solid tumors, particularly in melanoma, where more than 50% of patients achieved confirmed responses, researchers reported at the November 2024 American Society for Immunotherapy of Cancer Annual Conference in Houston, Texas.
In a clinical trial of 70 participants with recurrent or refractory solid tumors, the objective response rate was 57%, with a confirmed objective response rate of 51%, based on RECIST criteria, said Martin Wermke, MD., National Center for Tumor Diseases, University Hospital Carl Gustav, Dresden, Germany.
Specifically, among patients with melanoma (including cutaneous, uveal, mucosal and unknown primary melanomas), the confirmed objective response rate was ORR was 58% or 14 of 24 melanoma patients, he said.
“Especially remarkable was the response rate for uveal melanoma, a difficult-to-treat disease, where 6 out of 10 patients showed a confirmed response,” Dr. Wermke said at a press conference.
He also reported that 33 or 37 patients or 89% of patients with different types of tumors, including cutaneous melanoma, uveal melanoma, mucosal melanoma, ovarian cancer, synovial sarcoma, breast angiosarcoma, breast cancer, and small cell lung cancer, achieved a reduction in tumor size.
During his oral presentation on November 8, Dr. Wermke highlighted that the responses tended to be durable. He said, “Currently, the median duration of response in melanoma patients is 12.1 months with several responses persisting for more than 2 years, including one of our patients who achieved a PET negative, metabolic complete response of his melanoma.”
ACTengine IMA203 is a personalized T cell therapy that has been genetically modified to specifically target PRAME, a protein commonly found in solid tumors such as melanoma, lung, and gynecological cancers, the researchers explained.
PRAME is an excellent target because it is highly prevalent in many cancer types, and it is characterized by a high concentration of target molecules that are consistent and uniform, noted Dr. Wermke. More importantly, PRAME has a clean expression profile that is rarely found in healthy adult human tissue; therefore, the treatment can specifically target and treat the tumor while minimizing damage to healthy cells, he said.
Researchers found that any adverse effects that did occur were manageable, with the most common issue being chemotherapy-related cytopenia, affecting all patients.
Other adverse effects that were expected were mild to moderate cytokine release, experienced by 76.3% of patients in the study; about 11% of patients had grade 3 or greater cytokine release syndrome; no patient exhibited grade 4 cytokine release syndrome.
About 4% of patients had a grade 3 Immune Checkpoint-Associated Neurological Syndrome (ICANS), with no severe cases of neurotoxicity reported.
“We do see a little bit of neurotoxicity, but it’s quite infrequent, much less frequent than with CAR T cell products,” said Dr. Wermke.
Adult patients with recurrent or refractory solid tumors who had exhausted all available standard of care treatments were eligible for the Phase1a/1b study. They also were required to test positive for the HLA-A*02:01+ genotype and PRAME through central testing, have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1. no active brain metastases, with no serious autoimmune disorders or receiving ongoing immunosuppressive treatments.
The research team enrolled 28 patients in the first stage of the Phase 1a dose escalation trial. Following leukapheresis, T cells were modified to contain a T-cell receptor targeting PRAME and were grown in a controlled environment outside the body. Subsequently, the individuals underwent lymphodepletion with chemotherapy, followed by the infusion of IMA203 (dose level 1-4) and low-dose interleukin-2 administration for a specified duration – 1 million international units (IU) daily for 5 days, with twice-daily administrations for an additional 5 days. Once all patients completed the safety assessments at various dose levels, an additional 42 patients were enrolled in a Phase 1b dose expansion study
Dr. Wermke said the results showed promising efficacy outcomes for IMA203 in treating solid cancer patients, with manageable side effects and encouraging response rates in different cancer types. Additionally, he noted that the phase 3 trial was set to start by the end of 2024.
The study was supported by Immatics, Tuebingen, Germany.
– By Cara Gallo Massey
Cara Gallo Massey is an experienced journalist and content creator specializing in healthcare, holistic wellness, and medicine. She is a frequent contributor to HealthTech Hotspot. Her articles on subjects ranging from cancer prevention and treatment, longevity, medical imaging, nutrition, and more have appeared in a wide range of national magazines, local media, and professional consumer publications. During her career, she has also been the features editor for The National Enquirer, The Star, and The Globe, as well as a frequent contributor to women’s, luxury lifestyle, and professional medical publications.
