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Johnson & Johnson: BCMAxCD3 bispecific antibody
Johnson & Johnson: BCMAxCD3 bispecific antibody. BCMAxCD3 bispecific antibody! Johnson & Johnson teclistamab subcutaneous injection for the treatment of relapsed/refractory multiple myeloma: total remission rate of 73%!
Jansen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced the latest results of the first phase I human dose escalation study (NCT03145181) of teclistamab (JNJ-64007957, JNJ-7957) at the 62nd Annual Meeting of the American Society of Hematology (ASH). This study evaluated patients with relapsed or refractory multiple myeloma (RRMM) who had previously been over-pretreated (heavily-pretreated) with teclistamab.
The results showed that: at the recommended subcutaneous (SC) phase 2 dose (RP2D), the overall response rate (ORR) of teclistamab treatment was 73% (n=16/22). The results of the SC formulation support the recommended dose for the key Phase 2 registration trial, which has already started. In addition, the latest results of intravenous (IV) preparations confirm the durability of remission.
teclistamab is a bispecific antibody targeting B cell maturation antigen (BCMA) and T cell CD3 receptor. The expression level of BCMA on multiple myeloma cells is significantly increased, and CD3 is involved in activating T cells. teclistamab redirects CD3 T cells to BCMA-expressing myeloma cells to induce cytotoxicity against target cells. Preclinical research results show that teclistamab can kill myeloma cells from over-pretreated patients.
Currently, teclistamab is evaluating the efficacy of treating relapsed or refractory multiple myeloma (RRMM) in a phase I clinical study, and is also exploring in a joint study. The production and development of teclistamab follows the license agreement signed by Janssen Biotechnology and Genmab to use the DuoBody® technology platform.
Dr. Alfred Garfall, assistant professor of medicine at the Perelman School of Medicine at the University of Pennsylvania, the ASH conference speaker, said: “Today’s subcutaneous preparation data is based on the very promising results of intravenous preparations earlier this year. The initial efficacy, including remission Persistence and initial safety in this highly pre-treated population are very encouraging and support further research on teclistamab in patients with relapsed or refractory multiple myeloma who require additional treatment options.”
Dr. Yusri Elsayed, Global Head of Hematology Malignancies at Janssen Research and Development, said: “We are committed to exploring promising treatment options in the treatment of multiple myeloma, including bispecific antibodies, such as teclistamab, that provide therapeutic response through antigen targeting. Our research on multiple myeloma is very extensive and we explore multiple targets through multiple channels. We will continue to look for new treatment options, especially for patients who relapse after treatment with existing therapies or who are not sensitive to existing therapies.”
The Phase I study announced at the ASH Annual Meeting included multiple myeloma that had relapsed after treatment with existing therapies or refractory to these therapies, and had previously received proteasome inhibitor (PI) and immunomodulatory drugs (IMiD) treatments patient. Before starting the study, the median number of treatment options received by patients was 6 (range 2-14); 92% had received Type 3 therapies, 86% were refractory to the last therapy, and 80% were refractory to Type 3 therapies 41% are refractory to five drugs, which means that the patient’s cancer does not respond to treatment with ≥2 immunomodulators, ≥2 PI, and 1 anti-CD38 therapy or recurs within 60 days of treatment. Patients with multiple myeloma refractory to three types of therapies and five types of drugs have poor survival prognosis due to limited treatment options.
The study is divided into two parts: dose escalation (part 1) and dose expansion (part 2). teclistamab RP2D has been determined to be 1500μg/kg SC, and the maximum tolerated dose has not yet been determined. Under the RP2D SC regimen, 55% of patients achieved very good partial remission (VGPR) or better remission (12/22), and 23% of patients (5/22) achieved complete remission (CR) or better remission . With a median follow-up of 3.9 months (range: 1.7-7.4 months), 94% (15/16) of patients in remission were still alive and disease-free. Under the RP2D SC program, the remission performance is durable and deepens over time.
Among the 11 patients with CR and assessable minimal residual disease (MRD) in all IV and SC cohorts, 8 patients got MRD negative CR under the 10-6 threshold, and 1 patient got MRD under the 10-5 threshold Negative CR. In the IV and SC cohorts, all 5 evaluable patients confirmed persistent MRD negative.
Under the SC RP2D regimen, 64% of patients had cytokine release syndrome (CRS) events. All of these events were grade 1 or 2 and were usually limited to gradual or gradual dose increases, and the first full dose. No patient discontinued treatment due to CRS. Among the 33 patients who received RP2D treatment, only one grade 1 reversible neurotoxic event was observed. The choice of 1500ug/kg SC-RP2D is based on good safety, effectiveness, pharmacokinetics and pharmacodynamic support. SC preparations may provide a lower dosing frequency than IV preparations, although current studies have not yet explored this.
In the SC cohort, the most common adverse events (AE; all grades ≥20%) of RP2D were CRS (64%), neutropenia (52%), anemia (39%), thrombocytopenia (33%), Leukopenia (33%) and fatigue (24%). At the RP2D SC dose, among patients with grade 3 and above adverse events (≥20%), the most common were neutropenia (33%) and anemia (21%). A grade 5 treatment-related adverse event (pneumonia) was reported at a dose of 80 μg/kg IV, but not at a dose of RP2D.