Novel Agent ADP-A2M4 Elicits Durable Response in Synovial Sarcoma

November 24, 2020
Nichole Tucker

Nichole Tucker, MA, is the Web Editor for Targeted Oncology. Tucker received her Bachelor of Arts in Mass Communications from Virginia State University and her Master of Arts in Media & International Conflict from University College Dublin.

The investigational engineered SPEAR T-cell agent, ADP-A2M4, induced durable responses in patients with synovial sarcoma, according to updated results from the phase 1 clinical trial presented during the Connective Tissue Oncology Society Annual Meeting.

The investigational engineered SPEAR T-cell agent, ADP-A2M4 (MAGE-A4), induced durable responses in patients with synovial sarcoma, according to updated results from the phase 1 clinical trial presented during the Connective Tissue Oncology Society Annual Meeting and simultaneously announced in a press release from Adaptimmune Therapeutics plc.

The median duration of response (DOR) was 28 weeks and 2 patients had ongoing responses beyond 72 at the time of data cutoff, September 1, 2020. The median overall survival has not been reached in the study. These data support the launch of the phase 2 SPEARHEAD-1 study (NCT04044768) of ADP-A2M4 as treatment of patients with advanced synovial sarcoma or myxoid/round cell liposarcoma.

“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,” said Dr. Brian Van Tine, associate professor of Medicine, Division of Oncology, Section of Medical Oncology, Washington University School of Medicine, in a statement.

Previously during the 2020 American Society of Medical Oncology (ASCO) Virtual Annual Meeting, efficacy and safety findings from the ADP-A2M4 trial were presented. Forty-four percent of patients had confirmed partial response to treatment per RECIST criteria, and 95% had disease control.

Based on the translational data from this study, induction of the IFNγ-related pathway by serum analyses was identified as an emerging biomarker of response for patients with synovial sarcoma. Additionally, the study revealed the MAGE-A4 expression and transduced cell dose were associated with reduction in tumor size.

The safety analysis showed a consistent event to those observed in patients with cancer to received lymphodepletion chemotherapy and cellular therapy. Events observed included low blood counts and cytokine release syndrome.

In the phase 2 study, 45 patients will be assessed for the primary end point of objective response rate and the key secondary end points of safety, best overall response, time to response, DOR, progression-free survival, and overall survival.

Patients with advanced synovial sarcoma or myxoid liposarcoma/myxoid round cell liposarcoma confirmed by cytogenetics will be eligible to enroll in SPEARHEAD-1 given they are between the age of 16 and 75 years old, have previously received an anthracycline or ifosfamide containing regimen, have measurable disease per RECIST v1.1, demonstrate MAGE-A4 expression in their tumors, have an ECOG performance status of 0 or 1, and have a left ventricular ejection≥40%.

In addition to sarcomas, ADP-A2M4 is being investigation in melanoma, head and neck, urothelial, gastric, ovarian, and lung cancers. Once commercialized in synovial sarcoma, it will be the first drug of its kind in the United States,” stated Adrian Rawcliffe, chief executive officer, Adaptimmune Therapeutics.


Durable responses with ADP-A2M4 in synovial sarcoma with confirmed responses in 44% of patients and disease control rate of 94% presented at CTOS. New Release. Adaptimmune Therapeutics plc. November 19, 2020. Accessed November 20, 2020.