Talquetamab Wins Approval in Europe for Relapsed/Refractory Myeloma

August 22, 2023

The European Commission has granted conditional marketing authorization to talquetamab-tgvs monotherapy for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 3 prior therapies and have demonstrated disease progression on the last therapy.

The European Commission (EC) has granted conditional marketing authorization to talquetamab-tgvs (Talvey) monotherapy for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy.¹

The approval was supported by data from the phase 1/2 MonumenTAL-1 trial (NCT03399799; NCT04634552), which showed that at a median follow-up of 12.7 months, evaluable patients treated with 0.8 mg/kg of talquetamab once every 2 weeks (n = 145) experienced an overall response rate (ORR) of 71.7% (95% CI, 63.7%-78.9%), including a very good partial response (VGPR) or better rate of 60.8% and a complete response (CR) or better rate of 38.7%. The median duration of response (DOR) was not reached (95% CI, 13.0–not estimable [NE]), and an estimated 76.3% of patients maintained a response for at least 9 months.

At a median follow-up of 18.8 months, patients treated with 0.4 mg/kg of talquetamab once per week (n = 143) achieved an ORR of 74.1% (95% CI, 66.1%-81.1%). The VGPR or better and CR or better rates were 59.5% and 33.6%, respectively. The median DOR was 9.5 months (95% CI, 6.7-13.3). An estimated 51.5% of patients maintained a response for at least 9 months.

“As multiple myeloma progresses and patients cycle through treatments, the disease becomes more difficult to treat and remission periods shorten,” Maria-Victoria Mateos, MD, PhD, a consultant physician in hematology at the University Hospital of Salamanca, stated in a news release. “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.”

On August 9, 2023, the FDA granted accelerated approval to talquetamab for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.² That regulatory decision was also based on data from MonumenTAL-1.

The single-arm, open-label, multi-cohort, multicenter trial enrolled adult patients with relapsed/refractory multiple myeloma who received 3 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.¹

Phase 1 included dose-escalation and -expansion portions to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the bispecific antibody. In phase 2, patients were treated at the recommended phase 2 doses of subcutaneous talquetamab of 0.8 mg/kg once every 2 weeks or 0.4 mg/kg once per week with a primary end point of ORR.

Evaluable patients received a median of 5 (range, 2-17) prior lines of therapy.

The study also included a cohort of patients who received prior T-cell redirection therapy (n = 51). This group received a median of 5 (range, 3-15) prior lines of therapy, including a prior bispecific antibody (35.3%), CAR T-cell therapy (70.6%), or both (6%). At a median follow-up of 14.8 months, this group experienced an ORR of 64.7%, including a VGPR or better rate of 54.9% and a CR or better rate of 35.3%. The median DOR was 11.9 months (95% CI, 4.8-NE), and the 12-month overall survival rate was 62.9%.

Regarding safety, the most common adverse effects (AEs) included cytokine release syndrome (any grade, 77%; grade 3/4, 1.5%), dysgeusia (72%; 0%), hypogammaglobulinemia (67%; 0%), nail disorders (56 %; 0%), and weight loss (40%; 3.2%). The most common infections reported included upper respiratory tract infection (29%; 2.1%) and COVID-19 (19%; 2.9%).

Twenty-nine percent of patients experienced neurologic toxicities, including immune effector cell–associated neurotoxicity syndrome (ICANS; any grade, 10%; grade 3/4, 2.3%). AEs leading to treatment discontinuation included ICANS (1.1%) and weight loss (0.9%).

“Today’s EC decision 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,” Edmond Chan, MBChB MD (Res), senior director and EMEA Therapeutic Area lead of Hematology at Janssen-Cilag, said. “The high ORRs 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.”

References

European Commission approves Talvey (talquetamab), Janssen’s novel bispecific therapy for the treatment of patients with relapsed and refractory multiple myeloma. News release. Janssen. August 22, 2023. Accessed August 22, 2023. https://www.globenewswire.com/news-release/2023/08/22/2729299/0/en/European-Commission-Approves-TALVEY-talquetamab
FDA grants accelerated approval to talquetamab-tgvs for relapsed or refractory multiple myeloma. News release. FDA. August 9, 2023. Accessed August 22, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-talquetamab-tgvs-relapsed-or-refractory-multiple-myeloma