Talquetamab effective in relapsed/refractory multiple myeloma

16th January 2023

In a phase 1/2 trial talquetamab a bispecific antibody demonstrated robust efficacy in patients with relapsed/refractory multiple myeloma

Data presented by US researchers at the American Society of Haematology (ASH) conference in New Orleans, showed that talquetamab demonstrated robust efficacy and manageable safety in patients wit heavily pre-treated relapsed/refractory multiple myeloma.

Multiple myeloma is a malignancy of terminally differentiated plasma cells that typically presents with bone marrow infiltration of clonal plasma cells and monoclonal protein in the serum and/or urine. Multiple myeloma accounts for 10% of all haematological malignancies and the global incidence was found to be 160,000 in 2020 and with a mortality of 106,000. Although treatments have improved in recent years, a proportion of patients experience relapse as shown in a 2016 study of 511 patients, which found that 16.0% experienced early relapse, with median time to relapse of 8.0 months.

Talquetamab is a bispecific IgG4 antibody which binds to both the the G protein–coupled receptor, family C, group 5, member D (which is highly expressed on multiple myeloma (MM) cells plasma cells) as well as to CD38 receptors that are also highly and uniformly expressed on MM cells. In preclinical studies, talquetamab was found to be a promising novel anti-myeloma agent in relapsed/refractory MM. In MonumenTAL-1, a phase 1/2 trial, researchers collected safety, efficacy, pharmacokinetic and pharmacodynamic data and which was used to select two appropriate doses of talquetamab: 0.405 mg/kg subcutaneous (SC) weekly and 0.8 mg/kg SC every other week. In the data presented at ASH, researchers used both doses and recruited patients with relapsed/refractory disease with ≥3 prior lines of therapy. A step-up dosing schedule was used to mitigate the risk of severe cytokine release syndrome (CRS) and the primary endpoint was the overall response rate (ORR) based on independent committee review. Several secondary endpoints were used including the duration of response (DOR), the rate of complete response or better (≥CR) and progression-free survival (PFS) as well as the incidence of adverse events.

Talquetamab outcomes in relapsed/remitted disease

A total of 288 with median age was 67 years were included and of whom, 143, received the 0.405 mg/kg dose. Overall, patients had received a median of 5 prior therapies.

Among those receiving the 0.405 mg dose, the ORR was 73% and the median time to response was 1.2 months, the median time to complete response (CR) was 2.1 months and the median DOR was 9.3 months, with a median PFS of 7.5 months. The most common adverse events (AEs) were CRS (79%), dysgeusia (48%), anaemia (45%) and skin-related AEs (56%). Data for the 0.8 mg/kg patients was not given in the abstract.

The authors concluded that talquetamab demonstrated robust efficacy, adding that further phase 1 studies were in place to evaluate the drug in combination with other agents in patients with relapsed/refractory MM.

Citation
Chari A et al. Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1. Abstract 157, ASH, 2022

CHMP recommends conditional marketing authorisation for multiple myeloma monotherapy

22nd July 2022

The Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorisation for Tecvayli® (teclistamab).

Teclistamab is an off-the-shelf, T-cell redirecting bispecific antibody. It targets both B-cell maturation antigen, a marker found on multiple myeloma cells, and CD3, on T-cells.

It is recommended as monotherapy for adult patients with relapsed and refractory multiple myeloma (RRMM), who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.

In December 2021, the EMA granted accelerated assessment for teclistamab. Accelerated assessment reduces the timeframe for the CHMP to review a marketing authorisation application and is granted when a medicinal product is of major interest for public health and therapeutic innovation.

The CHMP recommendation is based on positive results from the multicohort, open-label, Phase I/II MajesTEC-1 study (NCT03145181 and NCT04557098), evaluating the safety and efficacy of teclistamab in adults with RRMM.

The latest findings from the study were presented at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting and published in The New England Journal of Medicine.

Teclistamab resulted in deep and durable responses in patients with triple-class exposed multiple myeloma (n=165). With a median follow-up of approximately 14 months (14.1), the overall response rate was 63% (95% CI: 55.2–70.4), with 39.4% having a complete response (CR) or better. Almost half (46%) of patients who achieved a CR or better were minimal residual disease-negative.

Adverse events (AEs) were consistent with this patient population and toxicities consistent with T-cell redirection were mostly Grade 1/2. The most common AEs were cytokine release syndrome and neutropenia. Infections were frequent (76.4%; 44.8% Grade 3 or 4). The overall incidence of neurotoxic events was low and five patients had immune effector cell-associated neurotoxicity syndrome. There were five treatment-related deaths, and dose reductions and discontinuations due to AEs were infrequent.