Afamitresgene Autoleucel Phase 2 Sarcoma Data, FDA Submission on Horizon


Based on findings from the SPEARHEAD-1 trial, Adaptimmune plans to submit a biologics license application to the FDA in 2022 for afamitresgene autoleucel to treat synovial sarcoma.

Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer

Adrian Rawcliffe

Adaptimmune announced that it will be presenting initial phase 2 data from the SPEARHEAD-1 trial exploring afamitresgene autoleucel (afami-cel, formerly ADP-A2M4) for synovial sarcoma and myxoid/round cell liposarcoma (MRCLS) at the ASCO Annual Meeting. Based on findings from this study, the company plans to submit a biologics license application (BLA) to the FDA in 2022, according to Adrian Rawcliffe, chief executive officer of the company.

The phase 2 trial was based on promising early findings, wherein the T-cell receptor (TCR) therapy afamitresgene autoleucel elicited a response in 44% of patients with synovial carcinoma. When including stable disease, the overall disease control rate was 94% with the cell therapy. At the latest data cutoff for the phase 1 study, which was September 1, 2020, the median duration of response was 28 weeks, with 2 responses ongoing beyond 72 weeks.

“The impact on patients treated with ADP-A2M4 is transformative, as they benefit from a durable response from a single treatment," Brian Van Tine, MD, PhD, from the Washington University School of Medicine and Siteman Cancer Center, said in a statement at the time of the data presentation. "This leads to the highest quality of life I have been able to provide patients with synovial sarcoma after treatment."

Afamitresgene autoleucel consists of autologous cells collected via leukapheresis, which are processed to isolate CD4 and CD8 cells. These T cells are then genetically modified using a lentiviral vector to express a MAGE-A4 specific TCR. The MAGE-A4 antigen is highly expressed in several solid tumors, suggesting broad applicability of the therapy. Once modified, the cells are expanded using CD3/CD28 beads followed by cryopreservation. Prior to administration, a lymphodepleting regimen is administered.

The phase 1 study enrolled 16 patients with synovial sarcoma. Overall survival data was available for 11 of the 16 patients treated with afamitresgene autoleucel, and a median was not yet reached at the time of the data cutoff. The adverse events seen in the study were similar to those expected with lymphodepleting chemotherapy. Cytokine release syndrome was also noted.

“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 United States in 2022,” Rawcliffe said when the phase 1 data were announced.

Upcoming findings from the phase 2 study will include data from 25 patients for preliminary efficacy. An additional 7 patients were enrolled in the study but did not have adequate follow up for the ASCO presentation. The abstract will be released on May 19, 2021, and additional findings will be announced June 4.

Based on earlier findings, afamitresgene autoleucel has received a regenerative medicine advanced therapy designation from the FDA along with a PRIME designation from the European Medicines Agency. These designations provide enhanced dialogue with regulatory agencies and are intended for cell and gene therapies that address serious or life-threatening diseases.

“This is only the beginning of the tremendous potential of our products targeting MAGEA4," Rawcliffe said. "We will rapidly pursue additional indications, starting with the phase 2 trial in gastroesophageal cancers with ADP-A2M4CD8 expected to initiate in the first half of 2021."

ADP-A2M4CD8 is a next-generation product also targeting MAGE-A4, which is under exploration in a phase 1 study known as SURPASS (NCT04044859). The study is intended for patients with MAGE-A4-expressing urothelial, head and neck, gastric, esophagogastric junction, non-small cell lung cancer, or esophageal cancer. Another therapy, ADP-A2AFP, geared toward the AFP protein is under exploration in liver cancer in a phase 1 study (NCT03132792). Early results from both studies were presented in 2020, with additional updates expected later this year, Rawcliffe noted.

In addition to these clinical findings, Adaptimmune also anticipates preclinical results at the American Society of Gene & Cell Therapy meeting for their new HLA-independent TCR therapy program. This program is being co-developed with Astellas.

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