Talquetamab has been granted a conditional marketing authorisation by the European Commission as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma.
Talquetamab (brand name Talvey) is approved as a weekly or biweekly subcutaneous injection after an initial step-up phase. It can be used as monotherapy for the treatment of patients relapsed and refractory multiple myeloma who have had an inadequate response to at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. They must also have demonstrated disease progression on the last treatment.
The treatment is a bispecific engaging antibody that binds to CD3, on the surface of T-cells, and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel target highly expressed on the surface of multiple myeloma cells and hard keratinised tissues.
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.
Commenting on the EC decision, Edmond Chan, senior director EMEA therapeutic area lead haematology, Janssen-Cilag Limited, said: ‘[This] brings a new off-the-shelf option, with a novel cellular target and the immediate option of biweekly dosing, to an area of high unmet clinical need.
‘The high overall response rates in patients with heavily pretreated multiple myeloma, including those with prior T-cell redirection therapy, are encouraging, and we believe talquetamab has the potential to offer physicians flexibility and versatility when determining the optimal treatment regimen for their patients.‘
The EC approval follows a similar FDA approval in the US in August 2023.
Talquetamab clinical efficacy
The talquetamab approval was based on efficacy data from the phase 1 and phase 2 MonumenTAL-1 study. In the trial, patients had received a median of five prior lines of therapy and talquetamab was given at a weekly dose of 0.4 mg/kg or biweekly 0.8 mg/kg.
For both dosage regimens, patients showed meaningful overall response rates. After a median follow-up of 12.7 months, 71.7% of response-evaluable patients treated at the 0.8 mg/kg biweekly dose achieved a response. Some 60.8% achieved a very good partial response (VGPR) or better and 38.7% achieved a complete response (CR) or better.
After a median follow-up of 18.8 months, 74.1% of response-evaluable patients treated with the 0.4 mg/kg weekly dose of talquetamab achieved a response; 59.5% a VGPR or better and 33.6% achieved a CR or better.
An estimated 76.3% and 51.5% of patients maintained a response for at least nine months at the 0.8 mg/kg biweekly and 0.4 mg/kg weekly talquetamab doses, respectively.
Maria-Victoria Mateos, consultant physician in haematology at the University Hospital of Salamanca in Spain, said: ‘As multiple myeloma progresses and patients cycle through treatments, the disease becomes
more difficult to treat and remission periods shorten. Targeting GPRC5D has been shown to deliver deep responses, and unlike many other targets for multiple myeloma, its expression is limited on immune cells providing an important new approach to targeting this heterogenous disease.‘
