Rare Daily Staff

Adaptimmune Therapeutics reported positive initial data from its phase 2 SPEARHEAD-1 trial of its engineered T cell therapy afami-cel in heavily treated pre-treated patients with synovial sarcoma in poster presentations at the American Society of Clinical Oncology meeting, which showed an overall response rate of 41.4 percent.

The company said the data will be presented in an oral presentation at the Memorial Sloan Kettering Cancer Center on June 4th.

“Initial data from SPEARHEAD-1 indicate that afami-cel has the potential to offer people with synovial sarcoma a promising new treatment option where there is currently a great unmet medical need,” said Sandra D’Angelo of the Memorial Sloan Kettering Cancer Center. “As clinicians, we want to be able to provide a treatment regimen that can help offer a better quality of life.”

At the time of data cut-off at the end of March, 37 patients had received afami-cel (32 with synovial sarcoma, 5 with myxoid/ round cell liposarcoma [MRCLS]). At that time, four patients were pending first efficacy assessment and 33 had at least one scan. The overall response rate was 39.3 percent (13 out of 33), 41.4 percent (12 out of 29) for synovial sarcoma, and 25.0 percent (one out of four) for MRCLS.

Of the 29 patients with synovial sarcoma with at least one scan, two had complete responses (CRs), 10 had partial responses (PRs), 13 had stable disease (SD), and four had progressive disease (PD).

The disease control rate for people with synovial sarcoma was 86.2 percent (25 out of 29), defined as either response or stable disease. Of the four patients with MRCLS with at least one scan, one patient had a partial response, two had stable disease, and one had progressive disease.

Adaptimmune said initial durability data is encouraging, and the median duration of response has not been reached. To date, the safety profile of afami-cel has been favorable, with mainly low-grade cytokine release syndrome and tolerable/reversible hematologic toxicities.

“Patients are seeing substantial benefit from afami-cel in SPEARHEAD-1 across a broad range of cell doses and levels of MAGE-A4 expression,” said Adrian Rawcliffe, Adaptimmune CEO. “We have shown a high response rate and these responses are still evolving in many patients with increasing depths of response over time and encouraging durability. I am confident that SPEARHEAD-1 will support our BLA submission next year and offer a life-changing treatment for people with synovial sarcoma.”

SPEARHEAD-1 is a phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of afami-cel. Afami-cel SPEAR T-cells target MAGE-A4+ tumors. MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02. Compelling clinical responses in patients with synovial sarcoma were previously reported with afami-cel in a phase 1 trial.

Approximately 90 patients are planned to be treated: 45 in Cohort 1 and 45 in Cohort 2. Enrollment in Cohort 1 is complete, and Cohort 2 is currently recruiting. The primary efficacy analysis will be for Cohort 1 only, which will be used to support the BLA filing in 2022. No formal hypothesis testing is planned for Cohort 2. Cohort 2 will strengthen the efficacy and safety database and will aid in descriptive sub-group analyses.

Eligible patients were between 16 and 75 years of age, HLA*02 positive with MAGE-A4 expression in greater than or equal to 30 percent of tumor cells that were ≥ 2+ by immunohistochemistry. Eligible patients received afami-cel doses between 1–10 × 10⁹ transduced T-cells after receiving lymphodepleting chemotherapy.

The primary endpoint is overall response rate per RECIST v1.1 by independent review. The primary endpoint will be evaluated using a one-sided exact-based Clopper-Pearson 97.5% confidence interval (CI). If the lower bound of the CI exceeds the response rate reported with historical second line therapy(ies), the trial will have met the pre-specified threshold for demonstrating efficacy.

An independent Data Safety Monitoring Board reviews ongoing safety and benefit/risk during the interventional phase of the trial.

Photo: Adrian Rawcliffe, Adaptimmune CEO

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