A CD30-targeted CAR T-cell therapy was found to elicit a high rate of durable complete responses (CRs) in heavily pretreated patients with relapsed/refractory Hodgkin lymphoma.
A CD30-targeted CAR T-cell therapy was found to elicit a high rate of durable complete responses (CRs) in heavily pretreated patients with relapsed/refractory Hodgkin lymphoma, according to data from 2 parallel phase 1/2 trials (NCT02690545; NCT02917083).1
Results from these studies, which were published in the Journal of Clinical Oncology, also showed that the product had a favorable safety profile in this patient population.2
Forty-one heavily pretreated patients received the CAR T cells; the median number of prior therapies was 7 , which included brentuximab vedotin (Adcetris), checkpoint inhibitors, and autologous or allogeneic stem cell transplantation.
Results showed that the most common adverse effects (AEs) reported were hematologic in nature and grade 3 or higher in severity. Moreover, cytokine release syndrome was reported in 10 patients, although all cases were determined to be grade 1. Notably, no neurologic toxicities were observed.
Additionally, in 32 patients with active disease who had previously received fludarabine-based lymphodepletion the ORR was 72%; this included a 59% CR rate (n = 19). At a median follow-up of 533 days, the 1-year progression-free survival (PFS) rate was 36% (95% CI, 21%-51%); the 1-year overall survival rate was 94% (95% CI, 79%-99%).
“These data are significant, as they demonstrate that CAR T-cell therapy may be a safe and effective treatment option for patients with Hodgkin lymphoma and potentially other lymphomas expressing the CD30 antigen,” Natalie Grover, MD, study co-author, assistant professor in the Department of Medicine, and a member at University of North Carolina (UNC) Lineberger Comprehensive Cancer Center, stated in a press release.
In the first phase 1/2 study, investigators set out to identify a safe dose of ATLCAR.CD30 cells to infuse following lymphodepleting chemotherapy and to obtain an estimation of the number of patients who would not experience disease progression for the 2 years following treatment with the CAR T-cell product. Additionally, they evaluated other effects of the ATLCAR.CD30 cells on the cancer.3
In the trial, adults received a dose of 1 x 108 cells/m2 of ATLCAR.CD30 cells, while children received 2 x 108/m2. Two independent dose-escalation sequences were run: 1 for adult participants and 1 for children. The study used the 3+3 design and begin with a low dose of 1 x 108 cells/m2. If no dose-limiting toxicities (DLTs) were observed in the first 3 patients evaluated, then the dose was raised to 2 x 108/m2. If toxicity was observed in 1 of the 3 patients in the initial treatment group, investigators would then expand enrollment to 6 patients. If DLTs were observed at the 2 x 108/m2 dose, then the dose will be reduced to that of 1.5 x 108 cells/m2.
The phase 2 portion of the trial aims to enroll a total of 31 patients. The primary end points of the trial include the number of participants with AEs in both adult patients and children and the 2-year PFS benefit following administration of the CAR T-cell therapy in both adult and children with CD30-positive relapsed/refractory Hodgkin lymphoma and non-Hodgkin lymphoma.
In the second phase 1, dose-escalation study, referred to as RELY-30, patients were started on the lowest of 3 doses of the CAR T cells.4 Once the dose schedule tolerable, the next group of patients are started at a higher dose of treatment; this will continue until all 3 doses of the product are evaluated. If the toxicity is determined to be intolerable, the dose will be reduced, or the infusions will be discontinued.
Patients will receive 1 injection of the CAR T cells on day 0. If the patient has stable disease at week 8 post infusion, then they can receive up to 6 additional doses of the T cells at 8- to 12-week intervals. After each infusion, the participant will undergo monitoring. If the participant had not previously undergoneautologous transplant, they will be given cyclophosphamide and fludarabine prior to their first infusion.
The primary end point of this trial is the number of patients with DLTs, while secondary end points included median number of T cells transduced with the vector, ORR, and mean number of T cells transduced with the vector.
“The highest-dose treatment led to the complete disappearance of tumors in the majority of patients, and almost all subjects had clinical benefit,” Carlos A. Ramos, MD, study co-first author and professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children’s Hospital, added in the release. “As such, we believe further study of this treatment approach is warranted.”
Tessa Therapeutics is working with Baylor College of Medicine and the UNC Lineberger Comprehensive Cancer Center to confirm the results yielded from these trials in another regulatory phase 2 trial, which is planned to launch in 2020.
“Longer term, we seek to explore the potential of this therapy beyond Hodgkin lymphoma to CD30-positive expressing non-Hodgkin lymphomas, where there is a demonstrated unmet need,” Ivan D. Horak, MD, president of research and development at Tessa Therapeutics, stated in the release.