On May 19, 2021Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell therapy to treat cancer, reported that kit will report initial data from its Phase 2 SPEARHEAD-1 trial, with afamitresgene autoleucel (afami-cel, formerly ADP-A2M4), at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) congress (Press release, Adaptimmune, MAY 19, 2021, View Source [SID1234580334]). Full abstracts were released online today. Data will be presented in an oral presentation by Dr. Sandra D’Angelo of the Memorial Sloan Kettering Cancer Center (Abstract #11504) on June 4th.
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"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 Chief Executive Officer. "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."
"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 Dr. Sandra P. 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."
SPEARHEAD-1 data will be presented at the time of the oral presentation scheduled for June 4th during the sarcoma session taking place from 1:30 p.m. to 4:30 p.m. EDT.
Afami-cel is efficacious and well-tolerated in heavily pre-treated patients based on initial data
At the time of data cut-off (March 29, 2021), 37 patients had received afami-cel (32 with synovial sarcoma, 5 with myxoid/ round cell liposarcoma [MRCLS])
Of the 37 patients who had received afami-cel, 4 patients were pending first efficacy assessment, and 33 had at least one scan as of data cut off (29 with synovial sarcoma, 4 with MRCLS)
The overall response rate1 was 39.3% (13/33), 41.4% (12/29) for synovial sarcoma; 25.0% (1/4) for MRCLS
Of the 29 patients with synovial sarcoma with at least one scan, 2 had complete responses (CRs), 10 had partial responses (PRs), 13 had stable disease (SD), 4 had progressive disease (PD)
The disease control rate for people with synovial sarcoma was 86.2% (25/29) (defined as either response or stable disease)
Of the 4 patients with MRCLS with at least one scan, 1 patient had a partial response, 2 had stable disease, and 1 had progressive disease
Objective responses have been reported across a wide range of cell doses and MAGE-A4 antigen expression levels
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.
Overview of SPEARHEAD-1 trial design
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 (CTOS 2020).
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 next year. 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 ≥ 16 and < 75 years, HLA*02 positive with MAGE-A4 expression in ≥ 30% 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.