Phase I Afami-cel study shows noteworthy responses in synovial sarcoma

Afamitresgene autoleucel (afami-cel; formerly ADP-A2M4), an adoptive T-cell receptor (TCR) therapy targeting the cancer antigen MAGE-A4, has achieved clinically meaningful results for patients with multiple solid tumor types in one Phase I clinical trial conducted by investigators at the University of Texas MD Anderson Cancer Center.

The results, published today in Medicine of Nature, were particularly notable in the subgroup of patients with synovial sarcoma, where afami-cel achieved a 44% objective response rate compared with a 24% overall response rate across all cancer types. Initial data from this study were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.

According to principal investigator David S. Hong, MD, professor of Investigational Cancer Therapeutics, these early results demonstrate proof of concept for this new cell therapy approach in solid tumors.

“These high response rates are significant because patients with synovial sarcoma have very few options after high-dose ifosfamide chemotherapy,” Hong said. “The overall toxicity of afami-cel was manageable, and we saw evidence of early activity in other cancer types. These results suggest that this is an approach with the potential to work in solid tumors where there are currently no approved cell therapies.”

The goal of TCR therapies is to more accurately target solid tumor cells without the toxicities to normal cells often associated with chimeric antigen receptor (CAR)-based cell therapies. Unlike CAR-based cell therapies, which recognize targeted surface proteins, TCR therapies such as afami-cel can target proteins normally present within the cell. Using the native T cell receptor, TCR therapies can recognize protein fragments, in this case from MAGE-A4, bound to immune-related proteins on the cell surface.

A total of 38 patients were treated with afami-cel in the study, with an average of three prior lines of therapy. Participants were 58% male; 92% of the participants were white and the rest were Asian. The study included 16 patients with synovial sarcoma, nine with ovarian cancer, three with head and neck cancer, two each with esophageal cancer, non-small cell lung cancer, urothelial cancer, and myxoid/round cell liposarcoma, and one each with gastric cancer and melanoma.

All patients experienced treatment-related adverse events, with low blood cell counts (lymphopenia, leukopenia, neutropenia, anemia, and thrombocytopenia) being the most common. Prolonged persistent cytopenia occurred at four weeks after treatment with Afami-cel in 17 patients (45%). Two patients experienced study-related deaths, resulting in lowering of the maximum age at screening and discontinuation of use of the high-dose cyclophosphamide lymphodepletion regimen.

The median duration of response was 26 weeks in all patients and 28 weeks in the synovial sarcoma subgroup. These findings in synovial sarcoma led to an ongoing Phase II study of affami-cel for patients with advanced synovial sarcoma or myxoid/round cell liposarcoma, also led by MD Anderson.

Early results from afami-cel have led to another Phase I study, also led by Hong, evaluating the next generation of afami-cel, known as ADP-A2M4CD8. This new TCR therapy expresses a CD8 co-receptor with the aim of broadening the immune response in solid tumors. Hong shared encouraging early data from that trial at the European Society of Medical Oncology (ESMO) Congress 2022.

These studies are part of an ongoing strategic alliance between MD Anderson and Adaptimmune, which aims to accelerate the development of new T-cell-based therapies in several types of cancer.

This study was supported by Adaptimmune.

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