Data from patients with a form of connective-tissue cancer who participated in a Phase I study of an investigational cell therapy lend support to an ongoing trial that could potentially be used to secure regulatory approval, the company developing the therapy said.
Oxfordshire, U.K.-based Adaptimmune Therapeutics announced Friday the presentation of data from the Phase I study of its T-cell receptor (TCR) therapy, ADP-A2M4, in patients with solid tumors previously treated with chemotherapy. Data from one cohort, of participants who had synovial sarcoma, support the ongoing Phase II SPEARHEAD-1 study’s use as the registration trial, said the company, which hopes to launch ADP-A2M4 in 2022. Adaptimmune also has operations in Philadelphia.
The company announced data from its study of the TCR, which targets MAGE-A4 in several solid tumors, with eight of the 16 synovial sarcoma patients achieving partial responses, including one whose response had not been confirmed. Although synovial sarcoma is rare, it constituted the largest cohort in the trial.
Other cohorts included patients with head and neck, esophagogastric junction, lung, melanoma and liver cancers, all with two to four patients. TCRs are adoptive cell therapies like CAR-Ts, but they work by targeting intracellular peptides rather than the cell-surface antigens that CAR-Ts target.
“This is probably the most impactful new therapy I’ve seen, not only because of the responses, but because of the durability of responses,” said Phase I investigator Dr. Brian Van Tine, an associate professor of medicine at Washington University in St. Louis, in a phone interview. Van Tine is also an investigator in SPEARHEAD-1, which is currently enrolling toward its goal of 60 patients with previously treated synovial or myxoid/round cell liposarcoma.
The data presented at ASCO showed a median duration of response lasting 28 weeks and a median progression-free survival of 20 weeks, while the median overall survival was not reached. As of their one-year assessments, three of the seven confirmed responders were continuing to benefit from therapy. The overall disease control rate was 90%.
“This TCR clearly shows that outside of lymphoma, there can be some benefit in solid tumors like synovial sarcoma,” said Dr. David Hong, deputy chair of The University of Texas MD Anderson Cancer Center’s department of investigational cancer therapeutics, in a phone interview. Hong, also an investigator, presented the data at ASCO.
Van Tine said the early data compare favorably with those seen among patients receiving standard treatments like the chemotherapy drug doxorubicin, which can produce some durable responses, but at the cost of high toxicity. According to the National Institutes of Health, synovial sarcoma generally has a survival rate of 50-60% at five years and 40-50% at 10 years, with recurrence reported up to five years and nine months after treatment and suggesting worse prognosis and low survival rates.
“It’s been fun to be part of this journey because watching the patients, it was just like night and day,” he said. “It must be like what being a breast cancer doctor or a lymphoma doctor is like.”
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