European Commission Approves TALVEY®▼ (talquetamab), Janssen’s Novel Bispecific Therapy for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma

Talquetamab, the first bispecific antibody targeting GPRC5D, showed an overall response rate of more than 70 percent with durable responses, including responses achieved by over 60 percent of patients with prior T-cell redirection therapy.^1,2

The Janssen Pharmaceutical Companies of Johnson & Johnson, announced today that the European Commission (EC) has granted conditional marketing authorisation (CMA) of TALVEY®▼ (talquetamab), as monotherapy for the treatment of 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.¹

Talquetamab is a bispecific T-cell 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 expressed on the surface of multiple myeloma cells and hard keratinised tissues, with minimal to no expression detected on B-cells and B-cell precursors.¹ Talquetamab is approved as a weekly (QW) or biweekly (Q2W) subcutaneous (SC) injection, after an initial step-up phase.¹

Dr Patrick Hayden, Consultant Haematologist and clinical lead for the myeloma service, at St. James’s Hospital said: “Patients with relapsed and refractory multiple myeloma typically experience frequent changes of treatment, short remissions and poor outcomes.³ Every patient’s disease is unique and requires a treatment strategy tailored to their specific needs. The approval of talquetamab represents an important advance for patients living with this difficult-to-treat blood cancer, as this novel compound has a new cellular target called GPRC5D. This approach has been shown to deliver deep responses in patients with advanced myeloma, many of whom were heavily pre-treated.”

The CMA was supported by positive results from the Phase 1/2 MonumenTAL-1 study (Phase 1: NCT03399799; Phase 2: NCT04634552), evaluating the safety and efficacy of talquetamab in patients with RRMM.4,5 The latest data from the study were recently presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (2-6 June, Chicago) and the 2023 European Haematology Association (EHA) Congress (8-11 June, Frankfurt).

Dr Thorsten Giesecke, General Manager, Commercial Business, Janssen Sciences Ireland UC, said: “Talquetamab’s approval reinforces our focus on strengthening our multiple myeloma offering by investing in cutting-edge research that will help us continue to improve patient outcomes and importantly, their quality of life. Once available in Ireland, Talquetamab will expand the range of therapeutic options available to clinicians when treating patients with advanced multiple myeloma, offering them flexibility for optimising treatment protocols. Janssen’s legacy in innovation and the development of treatments for multiple myeloma spans more than two decades and we are committed to delivering therapeutics which have the potential to transform clinical outcomes for Irish patients.”

Patients in the study (0.8 mg/kg Q2W: n=145; 0.4 mg/kg QW: n=143) had received a median of five (range, 2-17) prior lines of therapy and showed meaningful overall response rates (ORR) across both doses. With a median follow-up of 12.7 months, 71.7 percent (95 percent Confidence Interval [CI], 63.7-78.9) of response-evaluable patients treated at the 0.8 mg/kg Q2W dose achieved a response, 60.8 percent achieved a very good partial response (VGPR) or better and 38.7 percent achieved a complete response (CR) or better.1 With a median follow-up of 18.8 months, 74.1 percent (95 percent CI, 66.1-81.1) of response-evaluable patients treated with the 0.4 mg/kg QW dose achieved a response, 59.5 percent achieved a VGPR or better and 33.6 percent achieved a CR or better.1 Responses were durable with a median duration of response not reached (95 percent CI, 13-Not Estimable [NE]) in the 0.8 mg/kg Q2W dose group and 9.5 months (95 percent CI, 6.7-13.3) in the 0.4 mg/kg QW dose group.1 An estimated 76.3 percent and 51.5 percent of patients maintained a response for at least nine months at the 0.8 mg/kg Q2W and 0.4 mg/kg QW doses, respectively.¹

The MonumenTAL-1 study also included 51 patients with prior T-cell redirection therapy.2 Patients had received a median of five (3-15) prior lines of therapy, including prior exposure to a bispecific antibody (35.3 percent), CAR-T cell therapy (70.6 percent) or both (six percent).2 With a median duration of follow-up of 14.8 months, 64.7 percent of patients achieved a response, 54.9 percent achieved a VGPR or better and 35.3 percent achieved a CR or better.2 Median duration of response was 11.9 months (95 percent CI, 4.8-NE) and the 12-month overall survival rate was 62.9 percent.²

The most common adverse events (AEs) observed in the study were cytokine release syndrome (CRS; 77 percent, 1.5 percent Grade 3 or 4), dysgeusia (72 percent, all Grade 1 or 2), hypogammaglobulinaemia (67 percent, all Grade 1 or 2) and nail disorders (56 percent, all Grade 1 or 2).¹ In addition, 40 percent of patients experienced weight loss, including 3.2 percent with Grade 3 or 4 weight loss.¹ The most common infections were upper respiratory tract infection (29 percent, 2.1 percent Grade 3 or 4) and COVID-19 (19 percent, 2.9 percent Grade 3 or 4).¹ Neurologic toxicities were reported in 29 percent of patients, including immune effector cell-associated neurotoxicity syndrome (ICANS; 10 percent, 2.3 percent Grade 3 or 4).¹ Adverse reactions leading to treatment discontinuation were mainly due to ICANS (1.1 percent) and weight loss (0.9 percent).¹

The EC approval follows the U.S. Food and Drug Administration (FDA) approval of talquetamab for the treatment of adult patients with relapsed or refractory multiple myeloma who received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, in August 2023

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