Afami-cel Prompts Antitumor Immune Response in Synovial Sarcoma, Myxoid/Round Cell Liposarcoma

Afamitresgene Autoleucel (Afami-cel; AdaptImmune) induced peripheral and tumoral innate and adaptive immune responses in human leukocyte antigen (HLA) A*02-positive patients with advanced/metastatic synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS), according to a new analysis of phase 1 (NCT03132922) and 2 (SPEARHEAD-1, NCT04044768) trials.¹

Data from the analysis were presented at the American Associated for Cancer Research (AACR) Annual Meeting 2023, held April 14-19 in Orlando, Florida, by Martin Isabelle, PhD, Associate Director, Tumor Profiling and Mechanistic Biology, Translational Sciences, AdaptImmune.¹

“To support the continued investigation of potential mechanisms of durable anti-tumor activity, we previously showed that afami-cel induces broad and enduring peripheral cytokine responses and that afami-cel tumoral infiltration is associated with increased presence of activated and proliferative cytotoxic T-cells in the tumor microenvironment,” Isabelle and colleagues wrote in their poster.¹

Afami-cel consists of SPEAR T-cells, which use T-cell receptor-based recognition to target MAGE-A4+ tumors. Isabelle and colleagues analyzed 92 proteins across 68 patient samples and tumoral immune profiles from at least 15 patients, using immunohistochemistry staining, RNAscope technology, and immunofluorescence in their analyses. They found that serum from patients with controlled disease had an increase of markers associated with cytokine signaling and gene expression of adaptive and innate immune responses after afami-cel infusion compared to patients that had progressive disease. Looking at tumoral analyses, they observed a similar gene expression profile in patients with longer progression-free survival. Tumor biopsies revealed a relatively greater density of CD4+ and CD8+ T-cells, pro-immune M1 macrophages, and monocyte-derived dendritic cells after infusion compared to baseline, with a positive trend in responders compared to non-responders.

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“Afami-cel induces peripheral and tumoral innate and adaptive immune responses, a hallmark of durable anti-tumor activity. Following afami-cel infusion, a greater tumoral immune infiltrate was demonstrated at the gene and spatial protein levels compared with baseline,” Isabelle and colleagues wrote.¹ “RNA sequencing and serum analysis has elucidated some key insights into biological pathway activation, that encourages further investigation.”

The new analysis follows data published late last year that demonstrated continued clinical responses in patients with SS in the SPEARHEAD-1. The infusion was well-tolerated, and the total overall response rate was 36.5% (95% CI, 23.62-51.04), 38.6% (95% CI, 24.36-54.50) in SS and 25.0% (95% CI, 3.19-65.09) in MRCLS. 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%). 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. AdaptImmune is planning to soon submit a biologics license application based off the data.

“If you can find the right patient, and they can tolerate the conditioning, this is the nicest thing we can give to a sarcoma patient, because it's a single treatment. It's not ongoing chemotherapy once every 3 weeks. And if you can get 3 years out of a SPEAR T-cell, that's outstanding, because our basis for standard of care chemotherapy is 6 months. So, if you look at 6 months versus 3 years, this is truly an impactful therapy for the right patient," investigator Brian Van Tine, MD, PhD, professor of medicine and pediatrics, Washington University in St. Louis, previously told CGTLive™.

Click here to read more coverage of the AACR 2023 Annual Meeting.

REFERENCES

1. McAlpine C, Isabelle M, Broad R, et al. AfamitresgeneAutoleucel (Afami-cel; Formerly ADP-A2M4) demonstrates durable clinical responses by inducing broad immune engagement with anti-tumor activity. Presented at: AACR Annual Meeting 2023; April 14-19; Orlando, Florida.
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