Afamitresgene Autoleucel Induces Durable Clinical Response in Advanced Synovial Sarcoma Or Myxoid/Round Cell Liposarcoma

Afamitresgene autoleucel (afami-cel; formerly ADP-A2M4), a novel T-cell therapy, produced good clinical response lasting more than 4 years in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS), according to findings from cohort 1 of the ongoing phase 2 SPEARHEAD-1 trial (NCT04044768).¹

An independent review showed that afami-cel induced an overall response rate (ORR) of 38.6% in 44 heavily pre-treated patients with synovial sarcoma. The median duration of response was 50 weeks (range, 11.7-122).

Adaptimmune Therapeutics plans to use these findings to support a rolling biologics license application (BLA) for afami-cel in this patient population. The company expects to file the BLA later this year with an expected completion in mid 2023.

“With these results, we continue our excitement and optimism about the clear potential of afami-cel to address synovial sarcoma, a difficult-to-treat cancer with high unmet need,” Elliot Norry, MD, chief medical officer of Adaptimmune, stated in a news release. “These data reaffirm our commitment to this therapy, and we are very pleased to be able to include these data in our upcoming BLA submission.”

Afami-cel SPEAR T cells target MAGE-A4–positive tumors. MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02.

Investigators in the open-label SPEARHEAD-1 trial are evaluating the efficacy, safety, and tolerability of a single infusion of 1.0 x 109 to 10 x 109 afami-cel in approximately 90 patients. Cohorts 1 and 2 each include 45 patients.

The primary end point is ORR. Secondary end points include safety, patients with treatment-emergent adverse effects (AEs), serious AEs, efficacy, best overall response, time to response, duration of response, progression-free survival, and overall survival.

Investigators observed a treatment response across all evaluated subpopulations, including women, patients with elevated MAGE-A4 expression, those with lower disease burden at baseline, and those who did not require bridging therapy had higher response rates.

The median ORR was 36.2% (95% CI, 24.99%-48.68%) in pooled data from 69 patients presented at the 2022 ASCO Annual Meeting. The median duration of response was 52 weeks (95% CI, 18.56–not estimable).2

The results included 18 patients from cohort 1 and 51 from cohort 2, some of whom were included in a prior phase 1 trial (NCT03132922). All expressed 1 eligible HLA-A*02 allele. The median patient age was 42 years (range, 19-76). Patients received a median of 2 (range, 1-12) prior therapies and tumor MAGE-A4 H-score was 229.67 (range, 60.3–300).

Adaptimmune said these translational data show that afami-cel drives tumor infiltration of activated and proliferative cytotoxic T cells. This mechanism shifts the balance from immune-suppressive to a pro-immune in the tumor microenvironment, which likely contributes to antitumor response.

“We are on the cusp of an exciting and important time for people impacted by synovial sarcoma, a cancer that for much too long has not seen innovative treatment options,” study coauthor Brian A. Van Tine, MD, PhD, professor of Medicine and Pediatrics at Washington University School of Medicine in St. Louis, said in a news release. Van Tine presented the data at the 2022 Connective Tissue Oncology Society Annual Meeting.

“The SPEARHEAD-1 Trial results provide us a reason to be very optimistic about the game-changing potential to treat more people with this difficult cancer in the very near future."

References

1. Data from cohort 1 of SPEARHEAD-1 Trial at CTOS continue to support BLA submission for afami-cel in synovial sarcoma - response rate and durability remain consistent. News release. Adaptimmune Therapeutics. November 18, 2022. Accessed November 23, 2022. https://bit.ly/3gzQnJB
2. D’Angelo SP, Attia S, Blay J, et al. Identification of response stratification factors from pooled efficacy analyses of afamitresgene autoleucel (“Afami-cel” [Formerly ADP-A2M4]) in metastatic synovial sarcoma and myxoid/round cell liposarcoma phase 1 and phase 2 trials. J Clin Oncol. 2022;40(suppl 16):11562. doi:10.1200/JCO.2022.40.16_suppl.11562