Teclistamab (JNJ-64007957), a BCMAxCD3 Bispecific Antibody, Demonstrates 73% Overall Response Rate in Heavily Pretreated Relapsed/Refractory Multiple Myeloma Patients in Phase 1 Trial

December 09, 2020 /Bio ValleyBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced the latest results from the Phase I first-in-human dose-escalation study (NCT03145181) of teclistamab (JNJ-64007957, JNJ-7957) at the 62nd Annual Meeting of the American Society of Hematology (ASH). The study evaluated teclistamab in patients with relapsed or refractory multiple myeloma (RRMM) who had been heavily pretreated (defined as having previously received multiple treatment regimens).

Results showed that at the recommended Phase 2 subcutaneous (SC) dose (RP2D),The overall response rate (ORR) for teclistamab treatment was 73% (n=16/22).The results from the SC formulation support the recommended dose for the pivotal Phase 2 registration trial, which has already been initiated. Furthermore, the latest results from the intravenous (IV) formulation confirm the durability of response.

Teclistamab is a bispecific antibody targeting B-cell maturation antigen (BCMA) and the T-cell CD3 receptor.BCMA expression is significantly upregulated on multiple myeloma cells, and CD3 is involved in T-cell activation. Teclistamab redirects CD3+ T cells to BCMA-expressing myeloma cells to induce cytotoxicity against the target cells. Preclinical study results demonstrate that teclistamab can kill myeloma cells from heavily pretreated patients.

Currently, teclistamab is being evaluated for its efficacy in treating relapsed or refractory multiple myeloma (RRMM) in Phase I clinical studies and is also being explored in combination studies. The production and development of teclistamab adhere to the licensing agreement between Janssen Biotech, Inc. and Genmab for the use of the DuoBody® technology platform.

ASHMeetingDr. Alfred Garfall, Assistant Professor of Medicine at the University of Pennsylvania Perelman School of Medicine and the study’s lead investigator, stated: “Today’s data on the subcutaneous formulation build upon the highly promising results from the intravenous formulation reported earlier this year. The preliminary efficacy, including the durability of response, along with the initial safety profile in this heavily pretreated population, are very encouraging and support further investigation of teclistamab in patients with relapsed or refractory multiple myeloma who require additional treatment options.”

Janssen R&D Hematologic MalignanciesTumorDr. Yusri Elsayed, Global Head, stated, “We are committed to exploring promising therapeutic approaches in the treatment of multiple myeloma, including bispecific antibodies such as teclistamab, which deliver therapeutic responses through antigen targeting. Our research in multiple myeloma is extensive, investigating multiple targets via diverse mechanisms. We will continue to seek new treatment options, particularly for patients who have relapsed after or are refractory to existing therapies.”

The Phase I study presented at the ASH Annual Meeting enrolled patients with multiple myeloma who had relapsed after or were refractory to existing therapies, and who had previously been treated with proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). Prior to study initiation, the median number of previous treatment regimens was 6 (range, 2–14); 92% of patients had received three classes of therapy, 86% were refractory to their last line of therapy, 80% were triple-class refractory, and 41% were penta-drug refractory. This indicates that patients’ cancer showed no response to treatment with ≥2 immunomodulatory agents, ≥2 PIs, and one anti-CD38 therapy, or relapsed within 60 days of treatment. Patients with triple-class refractory and penta-drug refractory multiple myeloma have a poor survival prognosis due to limited treatment options.

The study was conducted in two parts: dose escalation (Part 1) and dose expansion (Part 2). The recommended phase 2 dose (RP2D) of teclistamab was determined to be 1500 μg/kg subcutaneously (SC); the maximum tolerated dose has not been established. Under the SC RP2D regimen, 55% of patients (12/22) achieved a very good partial response (VGPR) or better, and 23% of patients (5/22) achieved a complete response (CR) or better. With a median follow-up of 3.9 months (range: 1.7–7.4 months), 94% (15/16) of responding patients remained alive and progression-free. Under the SC RP2D regimen, responses were durable and deepened over time.

Among the 11 patients in the combined IV and SC cohorts who achieved complete response (CR) and were evaluable for minimal residual disease (MRD), 8 achieved MRD-negative CR at the 10⁻⁶ threshold, and 1 achieved MRD-negative CR at the 10⁻⁵ threshold. In the IV and SC cohorts, all 5 evaluable patients confirmed sustained MRD negativity.

Under the SC RP2D regimen, 64% of patients experienced cytokine release syndrome (CRS) events; all were Grade 1 or 2 and generally occurred during dose escalation or upon administration of the first full dose. No patients discontinued treatment due to CRS. Among the 33 patients treated at the RP2D, only one case of Grade 1 reversible neurotoxicity was observed. The selection of 1500 µg/kg SC-RP2D was based on favorable safety, efficacy, pharmacokinetic, and pharmacodynamic support. The SC formulation may allow for less frequent dosing compared with the IV formulation, although this has not been explored in the current study.

In the SC cohort, the most common adverse events (AEs; all grades ≥20%) at the RP2D were CRS (64%) and neutropenia (52%),Anemia(39%), thrombocytopenia (33%), leukopenia (33%), and fatigue (24%). At the RP2D SC dose, the most common grade ≥3 adverse events (≥20%) were neutropenia (33%) and anemia (21%). One case of a grade 5 treatment-related adverse event (pneumonia) was reported at the 80 μg/kg IV dose, but none were observed at the RP2D dose. (Bioon.com)

Original Source: Updated Results from the Phase 1 Study of the BCMAxCD3 Bispecific Teclistamab Show Preliminary Efficacy in Patients with Heavily Pretreated Relapsed or Refractory Multiple Myeloma