T-Cell Therapy Shows Promise in Rare Sarcomas

Afamitresgene autoleucel (afami-cel) induced responses in a third of patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS), according to results of the phase II SPEARHEAD-1 trial.

At data cutoff, the objective response rate (ORR) with the MAGE-A4-directed T-cell therapy was 34% per independent review, at 36% in the synovial sarcoma group and 25% in the MRCLS group, and the durability of response was "encouraging," said Brian Van Tine, MD, PhD, of Washington University School of Medicine in St. Louis.

Specifically, responses with afami-cel (formerly ADP-A2M4) persisted for more than 1 year in some patients, including 77 weeks for one, according to his presentation at the Connective Tissue Oncology Society (CTOS) virtual meeting.

"This is the first therapy I've worked on in a very long time where there is a clear response rate in synovial sarcoma that is durable," Van Tine told MedPage Today. "We usually don't speak in sarcoma of patients having durable response rates at week 77. This is well past a year for a single treatment."

Median duration of response had not been reached, and responses were ongoing in 75% of the responders, Van Tine reported.

"This is a response rate-driven trial, and the responses are quite durable," he said. "When you look at what most of our drugs are approved on, we're not looking at single treatment durability of a year or more, we're looking at [progression-free survival] improvements of 3 or 4 months. So, if you want to set a really high bar for approval in rare tumors, in my opinion this is hitting a really high bar for a response rate that is durable."

"And this is the highest quality of life I can give [a patient] when it works," he added. "And that is to do nothing afterwards."

SPEARHEAD-1 is an open-label, single-arm trial evaluating the anti-tumor activity of ADP-A2M4 SPEAR (specific peptide enhanced affinity receptor) T cells in patients who are HLA-A2-positive and have inoperable locally advanced synovial sarcoma or MRCLS expressing MAGE-A4.

The trial included 50 patients (42 with synovial sarcoma and eight with MRCLS); median age was 41 (range 19-73), and patients had received a median of three prior lines of therapy. Participants received a median dose of 8.5 billion transduced SPEAR T cells after receiving lymphodepleting chemotherapy.

A total of 47 of the 50 patients were evaluable on independent review, where all 16 responses were partial responses. Per investigator review, the ORR among the 50 patients was 34% (38.1% in the synovial sarcoma group and 12% in the MRCLS group), and included 15 partial responses and two complete responses. Median time to response was 4.9 weeks (range 4.1-12.0).

Disease control rates (stable disease plus responses) were 84% and 85% per investigator and independent review, respectively.

Treatment-related adverse events (AEs) were generally as expected, said Van Tine. As of data cutoff, 33 patients (66%) had experienced cytokine release syndrome (CRS), most grade 1/2 with one grade 3 case. Other grade 3 or higher AEs at week 4 post-infusion included cytopenia in 16%, neutropenia in 8%, anemia in 6%, and thrombocytopenia in 4%. For serious AEs of any grade, CRS was the most common at 6%.

Van Tine noted that the data will be used to support drug manufacturer Adaptimmune's biologics license application filing for afami-cel next year.

During the same CTOS session, Sandra P. D'Angelo, MD, of Memorial Sloan Kettering Cancer Center in New York City, presented a study showing that letetresgene autoleucel had clinical activity in patients with NY-ESO-1 (New York esophageal squamous cell carcinoma 1)-positive advanced MRCLS.

The two studies "really cement the role of engineered T-cell receptor therapy for MAGE-A4- and NY-ESO-1-antigen positive synovial sarcoma and MRCLS," commented session chair Breelyn A. Wilky, MD, of the University of Colorado Medicine in Aurora.

"I would argue now, based on this and prior presented data, that HLA screening as well as testing for both of these tumor antigens, should be performed for all metastatic and unresectable patients while beginning first-line chemotherapy," she said.

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