The FDA has granted a breakthrough therapy designation to teclistamab for the treatment of relapsed or refractory multiple myeloma.
The FDA has granted a breakthrough therapy designation to teclistamab for the treatment of relapsed or refractory (R/R) multiple myeloma (MM), according to a press release by Janssen.
Teclistamab is an off-the-shelf T-cell redirecting, bispecific antibody that targets both B-cell maturation antigen (BCMA) and CD3 receptors. Preclinical studies have found that the agent kills both myeloma cell lines in bone marrow-derived myeloma cells from heavily pretreated patients.
"We are pleased to have received breakthrough therapy and PRIME Designations for our novel bispecific antibody, teclistamab," said Peter Lebowitz, MD, PhD, global therapeutic area head, oncology, Janssen Research & Development, LLC, in a press release. "This program exemplifies our commitment to advancing science for patients living with multiple myeloma, and it builds upon our robust portfolio in this disease."
The breakthrough therapy designation is based on results of the phase 1 MajesTEC-1 study (NCT03145181), an open label randomized study which aims to determine the safety, efficacy, and phase 2 dosing suggestion for teclistamab. The study has an estimated enrollment of 204 participants and an estimated completion date of September 2024. The primary outcomes of the study are dose limiting toxicities (DLT) and the number of participants with adverse events (AEs). Secondary outcomes include teclistamab serum concentrations, the number of participants with teclistamab antibodies, preliminary antitumor activity, and biomarker assessment.
The study was split into 2 parts. The dose-escalation phase was made up of 2 arms. In arm 1, patients received teclistamab intravenously (IV), and in arm 2, they received the agent subcutaneously (SC). During the dose expansion portion, participants received the agent by IV in arm one and by SC in arm 2.
In order to participate, patients must have a documented diagnosis of MM, have measurable MM that is R/R to established therapies with known clinical benefit for R/R MM, have an ECOG score of o or 1, and must be able to sign an informed consent form. Patients with prior treatment with any BCMA-targeted therapy, toxicities from previous therapies that have not resolved to bassline levels or to grade 1 or less with the exception of alopecia or peripheral neuropathy, or has known active central nervous system involvement or exhibits the clinical signs or meningeal involvement of MM are not eligible to participate.
The agent is also being evaluated as a combination therapy in 3 separate studies. In the first phase 1 study, teclistamab is being evaluated in combination with talquetamab (NCT0458642). In the second phase 1 study, it is being evaluated in combination with daratumumab (NCT04108195). In the third phase 1 study, teclistamab is being evaluated with a number of different anti-cancer therapies such as daratumumab (Darzalex), pomalidomide (Pomalyst), lenalidomide (Revlimid), bortezomib (Velcade), and nirogacestat.
Full results of the MajesTEC-1 study will be presented on June 8, 2021 at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting.