- Cancer immunotherapy company Adaptimmune Therapeutics took a hit to its stock Wednesday, after announcing it would modify the preconditioning regimen for an ovarian cancer study testing its lead T-cell therapy.
- No objective responses had been observed to date in the initial segment of the Phase 1/2 open-label study testing Adaptimmune's NY-ESO SPEAR therapy, prompting the company to modify the trial.
- Adaptimmune will now add the chemotherapy fludarabine to the pre-conditioning regimen used to prepare patients for the T cell therapy. The combination of fludarabine and cyclophospamide is thought to help T-cell therapies expand and persist after infusion, but can be toxic as Juno Therapeutics saw in a trial this summer.
At the European Society for Medical Oncology meeting last week, Adaptimmune updated the data for its NY-ESO SPEAR T-cell receptor therapy in synovial sarcoma, which suggested adding fludarabine to cyclophosphamide helped trigger anti-cancer immune responses.
In one cohort of the synovial sarcoma study, Adaptimmune used cyclophosphamide alone, but the patients showed no response. Two other cohorts given both chemo agents fared better, prompting Adaptimmune to add fludarabine to its ovarian cancer study.
"Based on our clinical experience to date, we have amended the protocol for this trial to include both fludarabine and cyclophosphamide in the conditioning regimen," said Dr. Rafael Amado, Adaptimmune’s chief medical officer.
“We hope that, as previously observed in synovial sarcoma, this lymphodepleting regimen will enable anti-tumor immune responses mediated by NY-ESO SPEAR T cell therapy in these patients with advanced chemotherapy relapsed or refractory ovarian cancer."
Adaptimmune will enroll ten more women with treatment resistant or refractory metastatic ovarian cancer under the new trial protocol.
Adding fludarabine is not without risks, however. In Juno Therapeutics' study of its lead JCAR015 therapy, three patient deaths from cerebral edema were observed after fludarabine was added to the pre-conditioning regimen. Juno blamed the interaction between the flu/cy regimen with the JCAR015 cells for the deaths.
A fourth death from severe neurotoxicity was also seen in a separate Juno study which also involved fludarabine. After the Food and Drug Administration halted the JCAR015 trial, Juno removed fludarabine and was allowed to proceed, although that has set back its development timeline.
Adaptimmune's NY-ESO program is in development as part of the company's $500 million collaboration with GlaxoSmithKline. Clinical trials are under way in synovial sarcoma, multiple myeloma, ovarian cancer, melanoma, non-small cell lung cancer and esophageal cancer.
A pivotal study for synovial sarcoma is planned for 2017 while a Phase 3 study for myxoid round cell liposarcoma, — which hasn't started recruiting yet — is under a partial clinical hold with the FDA.