(P 202) IMPACT OF AFAMI-CEL ON THE HEALTH STATE OF PATIENTS WITH ADVANCED SYNOVIAL SARCOMA OR MYXOID/ROUND CELL LIPOSARCOMA: COHORT 1 OF SPEARHEAD-1

Objective: The autologous engineered T-cell receptor T-cell therapy afamitresgene autoleucel (afami-cel) targets tumors expressing melanoma-associated antigen A4 (MAGE-A4). In SPEARHEAD-1 (NCT04044859), the Phase 2 trial of a single infusion of afami-cel, patients with advanced synovial sarcoma (SyS) or myxoid/round cell liposarcoma (MRCLS) in Cohort 1 experienced response rates of 38.6% and 25.0% and median durations of response of 11.6 months and 4.2 months, respectively, with transient cytokine release syndrome and transient Grade ≥3 cytopenias occurring in >70% of patients.1 Here, we report the effects of afami-cel treatment on the overall health state and quality of life of these patients.

Methods: Afami-cel was infused into eligible patients following lymphodepletion chemotherapy. Eastern Cooperative Oncology Group performance status (PS) at baseline; Days 8, 15, 22, and 29; Weeks 6, 8, 12, 16, and 24; and Month 8 and then every 2 months thereafter, and EuroQol 5 Dimensions 3 Levels (EQ-5D-3L) at baseline and Weeks 8, 16, and 24 post infusion were recorded. Quality of life measures were pre-specified exploratory trial endpoints. EQ-5D-3L endpoints recorded by patients comprised the visual analogue score (VAS) rating of their overall health from 0–100, and if they had no, some, or extreme problems in five different domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Paretian Classification of Health Change (PCHC) over time and correlations with clinical response (assessed by Response Evaluation Criteria in Solid Tumors [RECIST] v1.1 by investigators) were also analyzed.

Results: Baseline PS was recorded for the 52 patients who received afami-cel in Cohort 1 (PS 0, patient fully active: n=27; PS 1, patient restricted in physically strenuous activity but still active: n=25). At the August 30, 2023, data cutoff, at Days 8 and 15 post infusion, 63% (30 of 48 recorded) and 75% (39 of 52 recorded) maintained or improved their PS, respectively, and 38% (18 of 48) and 25% (13 of 52) had a deterioration in PS from baseline. At Days 22 and 29, 78% (40 of 51 recorded) and 78% (38 of 49 recorded), respectively, maintained or improved their PS. Over Week 6 to Month 14, 87–100% of patients with reported PS who remained on study had an improved or maintained PS compared with baseline. The median EQ-5D-3L VAS health score improved to 80 at Week 24 (n=19) from 61 (n=45) at baseline. Kaplan-Meier analysis of time to next treatment or death showed a median of 5.7 months in the seven patients with worsening VAS, and 10.0 months in the 27 patients with stable or improving VAS. Of the 45 patients who completed the EQ-5D-3L domain analysis at baseline, 58% had some or extreme problems with anxiety/depression and 76% had some or extreme problems with pain/discomfort. Of the 34 patients who had both baseline and at least one subsequent time point in the EQ-5D-3L domain analysis, 59% had PCHC response of “better” at one or more time points following afami-cel infusion. The PCHC response showed a correlation with disease control as measured by RECIST v1.1.

Conclusion: The patient-reported outcomes in this small dataset suggest that afami-cel can positively impact the health status of patients with advanced SyS or MRCLS, with the clinical responses to afami-cel associated with maintenance or improvement in patients’ overall health and quality of life.

1. D'Angelo, SP et al. Lancet. 2024;403:1460–71.
These data were first reported at ESMO Sarcoma, Lugano, Switzerland, March 14–16, 2024.