The FDA has placed a partial clinical hold on a planned pivotal trial examining NY-ESO SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell therapy in patients with myxoid round cell liposarcoma (MRCLS), according to Adaptimmune Therapeutics, the company manufacturing the treatment.
Adaptimmune reported that the hold is not related to safety issues. In its notification of the hold, the FDA asked Adaptimmune questions related to the trial design and requested additional information on CMC (chemistry, manufacturing, and controls).
The hold will not affect patients, as the study is not yet active and no patients have been recruited.
“Adaptimmune is running a number of different studies with its NY-ESO program and continues to enroll patients in synovial sarcoma, ovarian, and lung cancer trials in the United States,” James Noble, CEO of Adaptimmune, said in a statement.
“We have been in dialogue with the FDA since achieving breakthrough status earlier this year and this partial clinical hold requires a number of questions to be answered before we can start a new MRCLS trial intended to be used for registration purposes. We will be providing a full response to the FDA shortly and will update the markets when we have further news to report,” added Noble.
In February 2016, the T-cell therapy received an FDA breakthrough therapy designation for the treatment of patients with inoperable or metastatic pretreated synovial sarcoma who harbor HLA-A*201, HLA-A*205, or HLA-A*206 alleles and whose tumors express the NY-ESO-1 tumor antigen. NY-ESO-1 is highly expressed in the majority of synovial sarcomas and MRCLS.
The breakthrough designation was based on a phase I/II trial in which the treatment induced a response rate of 50% in patients with unresectable, metastatic, or recurrent synovial sarcoma treated with prior chemotherapy.
In the key phase I/II study, 12 patients received lymphodepleting chemotherapy followed by treatment with T-cells engineered to recognize an HLA-A2 restricted NY-ESO-1 peptide. All patients had progressed following prior ifosfamide and/or doxorubicin therapy. The most recent presentation of the study results was in November 2015 at the Annual Meeting of the Society of Immunotherapy for Cancer (SITC).
Ten of the 12 patients received the target dose of 1 to 6 billion total engineered T cells. Among these 10 patients, 6 (60%) had a response. The 2 patients who did not receive the target dose did not have a response, so the overall response rate (ORR) for the 12 total patients was 50% (n = 6).
At the time of the SITC meeting, Adaptimmune noted in a statement that the ORR in the phase I/II trial compared positively with the historical 4% partial response rate observed with pazopanib (Votrient) in this patient population. Pazopanib is the only FDA-approved drug in this setting.
Ninety percent (9/10) and 75% (9/12) of the patients receiving the target or any dose, respectively, remained alive and in follow-up at the time of the data analysis. Survival data beyond 1 year are available for 5 of the 12 patients (42%) overall.
Forty-two percent (5/12) of patients who received any dose have survival data beyond 1 year.
Nausea, anemia, pyrexia, lymphopenia, and neutropenia, were the most common adverse events. Most of these events could be resolved within 30 days of treatment.
One-third (n = 4) of the 12 patients who had a response had cytokine release syndrome (CRS). Two patients had grade 3 CRS and there were no cases of grade 4 CRS.
In their conclusion, the authors of the poster presented at the SITC meeting noted, “The evidence of relapse seen in some patients provides rationale for testing of combination approaches or second generation T-cells designed to overcome the immune suppressive environment of selected tumors.”