Afamitresgene autoleucel was found be efficacious with favorable tolerability in heavily pretreated patients with advanced synovial sarcoma or myxoid/round cell liposarcoma, according to data from phase 2 SPEARHEAD-1 trial.
Afamitresgene autoleucel (afami-cel, formerly ADP-A2M4) was found be efficacious with favorable tolerability in heavily pretreated patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS), according to data from phase 2 SPEARHEAD-1 trial (NCT04044768).1
Results, which will be presented during the 2021 ASCO Annual Meeting, demonstrated that afami-cel induced an overall response rate (ORR) of 39.4% in the total study population. The ORR achieved with the agent was slightly higher in patients with synovial sarcoma (n = 12/29), at 41.4%). In patients with MRCLS, the ORR with afami-cel was 25.0% (n = 1/4).
“Patients are seeing substantial benefit from afami-cell in SPEARHEAD-1 across a broad range of cell doses and levels of MAGE-A4 expression,” Adrian Rawcliffe, chief executive officer of Adaptimmune, stated in a press release.2 “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.”
Afami-cel is comprised of autologous cells collected via leukapheresis, which are processed to isolate CD4 and CD8 cells. Using a lentiviral vector, the T cells are genetically altered to express a MAGE-A4–specific T-cell receptor. The MAGE-A4 antigen is highly expressed in many solid tumors, which could suggest broad applicability of the therapy. Once modified, the cells are expanded using CD3/CD28 beads; this is followed by cryopreservation. Before the administration of afami-cel, patients underwent a lymphodepleting regimen.
Earlier data from the phase 1 ADP-A2M4 trial showed that 44% (n = 7) of 16 patients with synovial sarcoma achieved a partial response (PR) per RECIST criteria, with 94% of patients (n = 15) experiencing disease control.3 The median duration of response (DOR) was 28 weeks, with 2 PRs ongoing beyond 72 weeks at the time of data cutoff. Moreover, 11 out of 16 patients were alive at the time of data cutoff and the median overall survival (OS) had not yet been reached.
The phase 2 trial was to examine the efficacy, safety, and tolerability of afami-cel in patients with synovial sarcoma and MRCLS. To be eligible for enrollment, patients needed to be 16 years of age or older and under 75 years; they also had to have an ECOG performance status of 0 or 1. Patients also needed to be HLA-A*02 positive, have MAGE-A4 expression, and have previously received an anthracycline- or ifosfamide-containing regimen.
The primary end point was ORR per RECIST v1.1 criteria and independent review, while secondary end points included DOR, time to response, progression-free survival, and OS. Investigators also examined adverse effects and toxicities of special interest.
At the time of the data cutoff of March 29, 2021, a total of 37 patients had been given afami-cel; 32 of these patients had synovial sarcoma and 5 had MRCLS. Of the 37 patients who were given the agent, 4 patients were pending their first efficacy assessment and 33 had at least 1 scan.
Additional data indicated that of the 29 patients with synovial sarcoma who had at least 1 scan, 2 achieved complete responses, 10 had PRs, and 13 had disease stability; 4 patients experienced disease progression. Among patients with synovial sarcoma, the disease control rate was 86.2% (n = 25/29). Among the 4 patients with MRCLS and at least 1 scan, 1 achieved a PR, 2 had stable disease, and 1 had progressive disease.
Notably, objective responses were observed across a wide range of cell doses and MAGE-A4 antigen expression levels. Moreover, the responses achieved with the agent appear to be durable, with a median DOR that has not yet been reached (range, 4.3+ to 38.0+).
Afami-cell was determined to have a favorable safety profile, with most treatment-emergent adverse effects (TEAEs) noted to be consistent with those typically experienced by patients with cancer who are receiving cytotoxic chemotherapy and/or immunotherapy.
Ninety-five percent of patients experienced any-grade TEAEs, while 92% had toxicities that were grade 3 or higher. Some of the TEAEs experienced with the agent were decreased lymphocyte count (84%, any grade; 84% grade 3 or higher), decreased neutrophil count (73%; 68%), decreased white blood cell count (68%; 62%), cytokine release syndrome (59%; 3%), and decreased platelet count (27%; 16%).
Adaptimmune Therapeutics plc announced that they plan to submit a biologics license application for afami-cell next year.