Janssen Presents Phase 1 Data of GPRC5DxCD3 Bispecific Antibody Talquetamab Showing 69% Overall Response Rate in Relapsed/Refractory Multiple Myeloma

December 09, 2020 /BioValleyBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced preliminary data from the first-in-human dose-escalation Phase I study of talquetamab (JNJ-64407564) for the treatment of relapsed or refractory multiple myeloma (R/R MM) at the 62nd Annual Meeting of the American Society of Hematology (ASH). The results showed thatAt the recommended phase 2 dose (RP2D) for subcutaneous (SC) administration, the overall response rate (ORR) with talquetamab treatment reached 69%.

Talquetamab is a first-in-class, the only bispecific antibody that simultaneously targets GPRC5D (a novel target in 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 in multiple myeloma, and CD3 is involved in T cell activation. Preclinical studies in mouse models have demonstrated that talquetamab induces T cell-mediated killing of GPRC5D-positive multiple myeloma cells by recruiting and activating CD3-positive T cells, and inhibitsTumorformation and growth.

Mount Sinai CancerClinical TrialAjai Chari, MD, Professor of Medicine and Director of the Multiple Myeloma Clinical Research Program at the Office, stated, “There is an urgent need for continued innovation in multiple myeloma treatment approaches, particularly for patients who have relapsed after other therapies; the results with talquetamab are encouraging. The overall response rate and safety data from the Phase I study support further investigation of talquetamab as monotherapy and in combination regimens in patient populations with limited therapeutic options.”

Janssen Research & Development, Hematologic MalignanciesTumorDr. Yusri Elsayed, Global Head, stated, “GPRC5D is a novel target for the treatment of multiple myeloma. As a bispecific antibody that binds to T cells by targeting CD3, talquetamab is emerging as a potential therapeutic option for heavily pretreated patients. Based on the preliminary efficacy, safety, pharmacokinetic, and pharmacodynamic data presented today, we are committed to fully exploring the potential of talquetamab in the treatment of multiple myeloma.”

Talquetamab (JNJ-64407564, image source: PMID:32040549)

The Phase I study presented at the conference enrolled 157 patients with multiple myeloma (MM) who had progressed on or were intolerant to any available therapies. The median number of prior treatment regimens was 6 (range: 2–20); 87% of patients were refractory to their last line of therapy, 82% were triple-class refractory, and 33% were penta-refractory (refractory to ≥2 immunomodulatory drugs, ≥2 proteasome inhibitors [PIs], and one anti-CD38 therapy). The study consisted of two parts: dose escalation (Part 1) and dose expansion (Part 2).

In the study, the therapeutic doses of talquetamab were: intravenous (IV) administration at 1–180 μg/kg and subcutaneous (SC) administration at 5–800 μg/kg. Results from Part 1 demonstrated that patients treated with talquetamab exhibited therapeutic responses across all dose groups; the median time from treatment initiation to first confirmed response was 1 month (range: 0.2–3 months) at all doses.

Preliminary results from subcutaneous (SC) and intravenous (IV) formulations demonstrate encouraging clinical activity against the GPRC5D target. GPRC5D is highly expressed on multiple myeloma cells and is associated with poor prognostic factors. At the recommended phase 2 dose (RP2D) for SC administration, the overall response rate (ORR) was 69% (9/13), with 39% of patients achieving a very good partial response (VGPR) or better.

The researchers identified the recommended phase 2 dose (RP2D) for subcutaneous (SC) administration as 405 μg/kg and concluded that SC administration may offer the opportunity for less frequent dosing compared to intravenous (IV) formulations. Treatment responses were observed in 6 out of 9 patients with triple-class refractory disease and in 2 out of 2 patients with penta-refractory disease. Pharmacokinetic results demonstrated target exposure levels at the RP2D. At the SC RP2D of 405 μg/kg, pharmacodynamic data showed sustained T-cell activation, cytokine production, and redistribution.

In this study, the adverse event (AE) with an incidence ≥25% in the SC cohort at the RP2D was neutropenia (42%). Following SC administration at the RP2D, cytokine release syndrome (CRS) was observed in 64% of patients; all cases were low-grade, with no Grade ≥3 CRS events. The median time to onset of CRS was 2 days post-dose, and the median duration of CRS was also 2 days. The incidence of neurotoxicity following SC administration at the RP2D was 5%, with no patients experiencing Grade ≥3 events.。(Bioon.com)

Original Source: Janssen Presents First Data from the Phase 1 Study of the GPRC5DxCD3 Bispecific Talquetamab in Patients with Relapsed or Refractory Multiple Myeloma