T-cell Therapy Showing Promise in Synovial Sarcoma Patients in Phase 1 Trial

T-cell Therapy Showing Promise in Synovial Sarcoma Patients in Phase 1 Trial
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ADP-A2M4, an investigational therapy that uses engineered immune cells to fight cancer, showed an acceptable safety profile and promising effectiveness in people with synovial sarcoma, a rare cancer that develops around the joints and tendons, new clinical trial data show.

The findings were presented at the Connective Tissue Oncology Society (CTOS) annual meeting by trial investigator Brian Van Tine, MD, PhD, of the Washington University School of Medicine. The oral presentation was titled, “Durable Responses in Patients with Synovial Sarcoma in the Phase I Trial of ADPA2M4 (MAGE-A4).

“The impact on patients treated with ADP-A2M4 is transformative, as they benefit from a durable response from a single treatment. This leads to the highest quality of life I have been able to provide patients with synovial sarcoma after treatment,” Van Tine said in a press release.

T-cells are a type of immune cell that have the capacity to kill cancer cells. ADP-A2M4 is an autologous T-cell therapy, a form of treatment in which a patient’s own T-cells are collected, engineered to make them better at killing cancer, and then returned to the patient. Specifically, ADP-A2M4 involves T-cells with an engineered T-cell receptor (TCR) that targets the cancer-associated protein MAGE-A4.

These new findings come from an ongoing Phase 1 clinical trial (NCT03132922), which is evaluating the investigational therapy in multiple types of solid tumors. The trial, which is sponsored by ADP-A2M4’s developer Adaptimmune Therapeutics, is still enrolling at sites across the U.S. and in Canada. More information can be found here.

As of a September data cutoff date, 16 people with synovial sarcoma had been treated with ADP-A2M4. Their median age was 49, and all had received prior chemotherapy (median of 2.5 regimens). Prior to receiving ADP-A2M4, patients underwent lymphodepletion, which aims to kill immune cells already in the body.

The study’s main goal is to evaluate the safety profile of the investigational therapy. Thus far, results have been positive. The most common severe side effects were low levels of blood cells, which is consistent with the lymphodepletion regimen. Most (81%) participants experienced an inflammatory condition called cytokine release syndrome, but in most instances these cases were mild or moderate in severity.

One patient died of severe anemia (low red blood cell levels).  After this death, the trial’s eligibility criteria and the treatment regimen used for lymphodepletion were modified.

Overall, seven (44%) of the patients responded to therapy, meaning their tumors got smaller after treatment. These responses were generally durable, lasting a median of 28 weeks (about six months). Two had ongoing responses that have lasted more than 72 weeks (nearly a year and a half).

An additional eight patients (50%) experienced stable disease with treatment, meaning no improvement or progression, amounting to a disease control rate of 94%.

Of the 16 participants, 11 are still alive, so that the median overall survival rate cannot yet be calculated.

Biological analyses indicated that patients whose tumors have higher MAGE-A4 expression are more likely to have more tumor reduction following treatment. Increased activity of an inflammatory signaling pathway called the interferon gamma pathway has also been associated with a better treatment response.

Adaptimmune is now running a pivotal Phase 2 trial (NCT04044768), called SPEARHEAD-1, to further evaluate ADP-A2M4 in people with synovial sarcoma. Results may support an application to regulatory authorities requesting the treatment’s approval for this indication. The trial is recruiting at various locations in North America and Europe; more information is available here.

“Data from this trial have enabled rapid execution of our pivotal trial, SPEARHEAD-1, and support our aim to commercialize ADP-A2M4 as the first engineered TCR T-cell product in the US in 2022,” said Adrian Rawcliffe, CEO of Adaptimmune.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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