Janssen’s Teclistamab Demonstrates Deep and Durable Responses with 65% Overall Response Rate in Heavily Pretreated Relapsed/Refractory Multiple Myeloma

May 26, 2021 /BioonBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announcedUniversal T-cell redirecting BCMA×CD3 bispecific antibody teclistamab(JNJ-64007957, JNJ-7957) Latest Results from the Phase I MajesTEC-1 Study (NCT03145181). This was the first-in-human dose-escalation study evaluating teclistamab, conducted in patients with relapsed or refractory multiple myeloma (RRMM) who had previously received multiple lines of therapy (heavily pretreated).

Subcutaneous (SC) formulation results showed that, with a median follow-up of 6 months, in a heavily pretreated patient cohort (n=40) with a median of 5 prior lines of therapy, at the recommended Phase 2 dose (RP2D),The overall response rate (ORR) with teclistamab treatment was 65%.（n=26/40），Very good partial response (VGPR) or better rate was 58%，The complete response rate (CR) was 40%.. Over time, profound and durable responses were observed in patients. Meanwhile, the subcutaneous formulation of teclistamab demonstrated a manageable safety profile.

Teclistamab is a bispecific antibody targeting B-cell maturation antigen (BCMA) and the T-cell CD3 receptor. BCMA expression is significantly elevated 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 target cells. Preclinical studies demonstrate that teclistamab can kill myeloma cells from heavily pretreated patients.

Mechanism of Action of Teclistamab

Currently, teclistamab is being evaluated in a Phase I clinical trial to assess its efficacy in the treatment of relapsed or refractory multiple myeloma (RRMM), and is also being explored in combination studies. The manufacturing and development of teclistamab are conducted pursuant to a license agreement between Janssen Biotech, Inc. and Genmab for the use of the DuoBody® technology platform.

Amrita Y. Krishnan, Principal Investigator and Director of the Multiple Myeloma Program in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, stated: "We reported the preliminary results of teclistamab at the ASCO 2020 Annual Meeting. The updated results have demonstrated continued deepening of responses, with a substantial proportion of patients achieving durable responses. Throughout the dosing interval, teclistamab maintained sustained exposure above target levels, and sustained T-cell activation was observed. With this latest follow-up data, we further demonstrate the favorable clinical efficacy of teclistamab in patients who had received multiple prior therapies."

Janssen Research & Development Hematologic MalignanciesTumorDr. Yusri Elsayed, Global Head, stated: “We remain committed to exploring promising treatment approaches in multiple myeloma, including off-the-shelf T cell-redirecting bispecific antibodies such as teclistamab. The reported efficacy data are highly encouraging, particularly the durability of deep responses, and support further investigation of teclistamab as both a monotherapy and in combination with other agents. Despite significant advances in the treatment of multiple myeloma over the past decade, substantial unmet medical needs remain. These results represent an important step forward that will enable us to address these needs and potentially offer a valuable alternative treatment option in the future.”

BCMA-Targeted Investigational MM Immunotherapy (Source: PMID: 31277554)

The primary objectives of the Phase 1 MajesTEC-1 study were to determine the recommended Phase 2 dose (RP2D, Part 1) and to evaluate the safety and tolerability of teclistamab at the RP2D (Part 2). As of March 2021, 157 patients with multiple myeloma refractory to, relapsed after, or intolerant of prior therapies had been enrolled in the study.

The data presented here are from 40 patients treated with the recommended Phase 2 dose (RP2D) of 1500 μg/kg administered subcutaneously (SC). These patients had a median of 5 prior lines of therapy (range: 2–11). All patients (100%) had received prior therapy across 3 drug classes: proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 antibodies. Sixty-five percent (n=26) had been treated with 5 specific drugs (2 PIs, 2 IMiDs, and 1 anti-CD38 antibody). Eighty-three percent (n=33) were triple-class refractory, 38% (n=15) were 5-drug refractory, and 83% (n=33) were refractory to their most recent line of therapy. Patients with triple-class and 5-drug refractory multiple myeloma have a poor survival prognosis due to limited treatment options.

Results from a median follow-up of 6 months (range: 1.2–12.2 months) showed that in this cohort (n=40), at an SC RP2D of 1500 μg/kg, the overall response rate (ORR) with teclistamab treatment was 65% (n=26/40).

The results showed that responses were sustained and deepened over time: 58% of patients achieved a very good partial response (VGPR) or better, and 40% achieved a complete response (CR) or better. The median time to first response was 1 month. The median duration of response (DOR) was not reached. With a median follow-up of 7.1 months (range: 3.0–12.2 months), median DOR remained not reached. Among responding patients (n=26), 85% (22/26) remained alive and continued treatment.

In Part 1 of the study, no dose-limiting toxicities were observed with subcutaneous teclistamab at the RP2D. Among patients treated at the RP2D, one case (1%) of Grade 1 neurotoxicity was reported. The most common adverse events at the RP2D were cytokine release syndrome (70%, all Grade 1/2) and neutropenia (65%; 40% Grade 3/4).

The latest safety, efficacy, pharmacokinetic, and pharmacodynamic data from this study confirmed the selection of 1500 μg/kg SC as the recommended phase 2 dose (RP2D) for the pivotal phase 2 registration trial of teclistamab. (Bioon.com)

Source: Janssen’s Updated Phase 1 Results for Teclistamab Suggest Deep, Durable Responses in Patients with Heavily Pretreated Multiple Myeloma