The CAR T therapy tisagenlecleucel missed its EFS endpoint in the phase 3 BELINDA trial for B-cell non-Hodgkin lymphoma.
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Tisagenlecleucel (Kymriah), a CAR T-cell therapy, did not significantly improve event-free survival (EFS) compared with standard of care (SOC), missing the primary end point of the phase 3 BELINDA trial (NCT03570892).1
The therapy was being evaluated in the second-line treatment of patients with aggressive B-cell non-Hodgkin lymphoma who had primary refractory disease or who relapsed within 12 months of frontline treatment.
The safety data proved to be consistent with what has previously been reported with the product.
Novartis shared plans to complete a full evaluation of these findings, and representatives are working with the trial investigators to present them at a future medical meeting.
“Patients with aggressive B-cell non-Hodgkin lymphoma who are refractory to first-line treatment are vulnerable and we are disappointed that the BELINDA study did not meet its primary end point in this setting,” Jeff Legos, executive vice president and global head of Oncology & Hematology Development at Novartis, stated in a press release. “[Tisagenlecleucel] continues to demonstrate durable responses in patients with certain advanced blood cancers in the third-line setting.”
The open-label, multicenter, phase 3 trial enrolled patients with histologically confirmed, aggressive B-cell non-Hodgkin lymphoma at relapse/progression or in partial response following frontline treatment.2 To be eligible for enrollment, patients needed to have relapsed or progressed within 1 year from their last dose of treatment with an anti-CD20 antibody– and anthracycline-containing frontline chemoimmunotherapy or they had to have been refractory. Moreover, patients needed to have an ECOG performance status of 0 or 1, acceptable organ function, and have leukapheresis material of non-mobilized cells available for manufacturing.
If patients previously received treatment with CD19-targeted therapy or a gene therapy product or systemic lymphoma-directed second-line anticancer therapy before randomization, or previously underwent allogeneic hematopoietic stem cell transplant (HSCT), they were excluded. Other exclusion criteria included active central nervous system involvement, clinically significant active infection, or certain cardiovascular conditions.
The primary end point of the trial is EFS, and key secondary end points include local investigator–assessed EFS, overall survival, overall response rate, duration of response, time to response, safety, and tolerability.
Study participants on the investigative arm received investigator’s choice of optional platinum-based chemoimmunotherapy followed by lymphodepleting chemotherapy and a single dose of tisagenlecleucel. Those in the control arm received SOC, which was comprised of investigator’s choice of salvage chemotherapy followed by high-dose chemotherapy in responding patients and autologous HSCT. Those on the control arm were allowed to cross over to receive the CAR T-cell product upon disease progression determined by a blinded independent review committee.
In August 2017, the FDA granted a regular approval to the CAR T-cell therapy for the treatment of patients up to age 25 years with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse.3 A year later, in May 2018, the FDA approved tisagenlecleucel for use in adult patients with relapsed or refractory large B-cell lymphoma following 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.4