Janssen's First-in-Class GPRC5DxCD3 Bispecific Antibody Talquetamab Demonstrates Deep and Durable Responses with 70% Overall Response Rate in Heavily Pretreated Relapsed/Refractory Multiple Myeloma

May 27, 2021 /BioonBIOON/ -- Janssen Pharmaceuticals, a Johnson & Johnson (JNJ) company, recently announced follow-up data from the MonumenTAL-1 (NCT03399799) Phase I first-in-human dose-escalation study evaluating the GPRC5DxCD3 bispecific antibody talquetamab (JNJ-64407564) for the treatment of relapsed or refractory multiple myeloma (R/R MM). Updated results with a median follow-up of more than 6 months showed: in patients with R/R MM who had received a median of 6 prior therapies, when administered subcutaneously (SC) at the recommended Phase 2 dose (RP2D),The overall response rate (ORR) for talquetamab treatment reached 70%., there is60% of patients achieved a very good partial response (VGPR) or better.. FromThe median time from treatment initiation to first confirmed response was 1 month.(Range: 0.2-3.8 months).

Talquetamab is the only off-the-shelf T cell-redirecting bispecific antibody targeting GPRC5D currently in clinical development.This drug is a first-in-class and the only bispecific antibody that simultaneously targets GPRC5D (a novel target on multiple myeloma) and CD3 (a surface receptor on anti-cancer T cells). GPRC5D (G protein-coupled receptor class C group 5 member D) is highly expressed on multiple myeloma, and CD3 is involved in T cell activation. Preclinical studies in mouse models demonstrated that talquetamab, by recruiting and activating CD3-positive T cells, induces T cell-mediated killing of GPRC5D-positive multiple myeloma cells and inhibitsTumorformation and growth.

GPRC5D is a novel target for the treatment of multiple myeloma. As a bispecific antibody that engages T cells by targeting CD3, talquetamab is emerging as a potential therapeutic option for heavily pretreated patients with relapsed/refractory multiple myeloma (R/R MM).

Jesus G. Berdeja, Principal Investigator of the MonumenTAL-1 study and Director of Myeloma Research at Sarah Cannon Research Institute/Tennessee Oncology, said: "Most who wereDiagnosisPatients with multiple myeloma will relapse during the course of the disease. In this study, patients had disease that progressed, relapsed, or was refractory after multiple prior therapies, highlighting a significant unmet need for novel treatments. We are encouraged that just six months after announcing the initial talquetamab results at this RP2D dose, we now have follow-up data demonstrating that treated patients achieved initial responses rapidly (0.2–3.8 months), with responses deepening for many patients on continued treatment, supporting further exploration of dual targeting of GPRC5D and CD3 in patients with multiple myeloma.”

Janssen Research & Development, LLCTumorDr. Sen Zhuang, Vice President of Clinical Research, stated: "These new, updated efficacy and safety data demonstrate that talquetamab is a highly promising candidate therapy for patients with multiple myeloma who have relapsed or are refractory after multiple prior therapies. As the only investigational bispecific antibody targeting the novel GPRC5D target, we are committed to comprehensively exploring talquetamab, including a novel subcutaneous dosing strategy for multiple myeloma."

talquetamab (JNJ-64407564, Image source: PMID: 32040549)

The MonumenTAL-1 study comprises two parts: dose escalation (Part 1) and dose expansion (Part 2). As of April 18, 2021, 184 patients with R/R MM had received talquetamab. The study results established the RP2D as 405 μg/kg SC once weekly. Among patients treated at the RP2D, the median age was 61.5 years (range, 46–80 years), and the median number of prior lines of therapy was 6 (range, 2–14). 87% (n=26) of patients were refractory to their most recent regimen; 77% (n=23) were triple-class refractory (proteasome inhibitor [PI], immunomodulatory drug [IMiD], CD38 antibody), 20% (n=6) were penta-drug refractory (2 PIs, 2 IMiDs, 1 CD38 antibody), and 27% (n=8) had previously received B-cell maturation antigen (BCMA)-directed therapy. Patients with triple-class and penta-drug refractory multiple myeloma have a poor survival prognosis due to limited treatment options.

With a median follow-up of 6.3 months (range: 1.4–12.2 months), results showed that at the RP2D of 405 μg/kg subcutaneously (SC) once weekly, talquetamab treatment achieved an overall response rate (ORR) of 70%, including 65% (15/23) in triple-class refractory patients and 83% (5/6) in 5-drug refractory patients. The median duration of response (DOR) was not reached. Among responding patients, 81% (17/21) continued treatment, indicating that at the RP2D, a substantial proportion of responders achieve durable responses that deepen over time. At the RP2D, pharmacodynamic data demonstrated sustained T-cell activation.

At the RP2D, the most common adverse events were cytokine release syndrome (73%; 2% Grade 3), neutropenia (67%; 60% Grade 3/4),Anemia(57%; 27% Grade 3/4) and olfactory dysfunction (60%; all Grade 1/2).

Infections were reported in 37% of patients (3% grade 3/4), neurotoxicity in 7% of patients (all grade 1/2), and skin-related adverse events in 77% of patients (27% nail disorders). In Part 1, no dose-limiting toxicities were observed at the RP2D. (Bioon.com)

Original Source: Janssen Presents Updated Data on First-in-Class Talquetamab at ASCO Suggesting Deep and Durable Responses in Heavily Pretreated Patients with Multiple Myeloma