New Afami-Cel Data to Support BLA Submission in Synovial Sarcoma

Afamitresgene autoleucel (afami-cel; Adaptimmune Therapeutics) has demonstrated continued clinical responses in patients with late-stage synovial sarcoma in the phase 2 SPEARHEAD-1 study (NCT04044768).¹

These new data were presented in an oral presentation at the Connective Tissue Oncology Society (CTOS) annual meeting taking place in Vancouver, BC, by primary investigator Brian A. Van Tine, MD, PhD, professor of medicine and pediatrics, Washington University School of Medicine in St. Louis, on Friday, November 18th.¹

"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," Van Tine said in a statement.² "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."

Afami-cel consists of SPEAR T-cells, which use T-cell receptor-based recognition to target MAGE-A4+ tumors. The data presented were from 52 participants enrolled in cohort 1 of SPEARHEAD-1.¹ These participants had a median age of 41 years (range, 19-73), were HLA-A*02 positive, had an ECOG performance status of 0 or 1 (with the exception of 1 patient with an ECOG status of 2), and had disease confirmed to have MAGE-A4 expression which has previously failed an anthracycline- or ifosfamide-containing regimen (median prior lines of therapy, 3 [range, 1-12]). Participants had mostly synovial sarcoma (n = 44; 84.6%) although 8 participants (15.4%) had myxoid/round cell liposarcoma (MRCLS). Participants were lymphodepleted prior to afami-cel infusion and long-term follow-up is to continue for 15 years. The primary endpoint is overall response rate (ORR).

By independent review, there were no complete responses, 19 partial responses (36.5%), 27 cases of stable disease (51.9%), and 6 cases of progressive disease (11.5%), for a total ORR of 36.5% (95% CI, 23.62-51.04). By disease, the ORR in synovial sarcoma was 38.6% (95% CI, 24.36-54.50) and the ORR in MRCLS was 25.0% (95% CI, 3.19-65.09). The median time to response was 4.9 weeks (range, 4.1-12.1), the median duration of response was 50.3 weeks (range, 11.7-122.0+) in synovial sarcoma and 18.2 weeks (range, 12.4-24.0) in MRCLS, with 8 responses ongoing as off the data cutoff date. Responses were similar among patients stratified by age, number of prior lines of therapy, dose, or cytokine release syndrome (CRS).

Afami-cel had an acceptable safety profile, with treatment-emergent serious adverse events in over 3% of patients. Most participants (n = 27; 71.2%) experienced CRS, although all cases but 1 were below grade 3. These cases of CRS took a median of 2 days to onset (range, 1-23) and resolved in a median of 3 days (range, 1-14); toclizumab was used in 19 cases (26.5%). Almost all participants had any cytopenia but these cases fell to 10 (19.2%) at 4 weeks post-infusion. One participant experienced immune effector cell-associated neurotoxicity syndrome below grade 3.

Investigators found that afami-cel facilitates the movement of cytotoxic T-cells into tumors, and responders had tumor microenvironments shift from being immunosuppressive to pro-immune. They also found that better responses were associated with lower M2 immunosuppressor macrophage to cytotoxic T-cell ratio after infusion and grater M1 pro-immune macrophages at baseline, which increase after infusion.

"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, Adaptimmune, added to the statement.² "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."

The SPEARHEAD-1 trial is ongoing, with cohort 1 having completed dosing and cohort 2 continuing to dose patients.¹ Data from cohort 1 will be used to support Adaptimmune’s biologics license application for afami-cel to treat synovial sarcoma.

REFERENCES

1. Van Tine BA, Araujo DM, Blay JY, et al. Final analysis from SPEARHEAD-1 cohort 1 of afamitresgene autoleucel (“Afami-cel” [formerly ADP-A2M4]) in advanced synovial sarcoma and myxoid/round cell liposarcoma. Presented at: 2022 CTOS Annual Meeting, November 16-19, 2022, in Vancouver, BC.
2. 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. https://finance.yahoo.com/news/data-cohort-1-spearhead-1-130000636.html