CHMP Recommends Talquetamab Monotherapy for R/R Multiple Myeloma

July 21, 2023

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended conditional marketing authorization of talquetamab for use as a single agent in adult patients with relapsed or refractory multiple myeloma who have previously received at least 3 therapies.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization of talquetamab (Talvey) for use as a single agent in adult patients with relapsed or refractory multiple myeloma who have previously received at least 3 therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody and have progressed on their last therapy.¹

The recommendation for the subcutaneous bispecific antibody is supported by findings from the phase 1/2 MonumenTAL-1 study (NCT03399799; NCT04634552).² At a median follow-up of 18.8 months, an overall response rate (ORR) of 74.1% was reported in response-evaluable patients who received the agent at a weekly dose of 0.4 mg/kg (n = 143); this included a very good partial response (VGPR) or better rate of 59.4%. At a median follow-up of 12.7 months, evaluable patients who received talquetamab at 0.8 mg/kg once every 2 weeks (n = 145) experienced an ORR of 71.7%; in this group, the VGPR or better rate was 60.7%.

In a separate cohort of patients who previously received T-cell redirection (TCR) therapy (n = 51), the agent induced an ORR of 64.7% at a median follow-up of 14.8 months, with a VGPR or better rate of 54.9%.

“With talquetamab, a novel bispecific antibody targeting GPRC5D, we look to build on our legacy of innovation and bring forward a vital new treatment option for patients with relapsed and refractory multiple myeloma, who have a poor prognosis,” Edmond Chan, MBChB, MD, senior director EMEA Therapeutic Area Lead Haematology at Janssen-Cilag Limited, stated in a press release.¹ “Today’s recommendation from the CHMP marks an exciting step for patients who continue to face the challenges of this difficult-to-treat blood cancer. We look forward to working with health authorities to bring talquetamab to patients in need across the region as soon as possible, while we continue our focus on enhancing a robust multiple myeloma portfolio of therapeutics and regimens.”

The first phase of the MonumenTAL-1 study enrolled patients with measurable multiple myeloma who were intolerant to or progressed on established therapies.² Patients needed to have an ECOG performance status of 0 or 1. For the second phase of the research, patients needed to have measurable multiple myeloma and have received 3 or more prior therapies, including at least 1 IMiD, at least 1 PI, and at least 1 anti-CD38 monoclonal antibody. Here, patients were required to have an ECOG performance status of 0 to 2.

Those enrolled in the phase 1/2 trial received subcutaneous talquetamab at the recommended phase 2 dose of 0.8 mg/kg biweekly or 0.4 mg/kg weekly with step-up doses.

ORR served as the primary end point of the trial, and secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, immunogenicity, and pharmacodynamics.

The median age of patients in the weekly and biweekly dosing cohorts was 67 years (range, 38-86); those in the prior TCR cohort were younger, with a median age of 61.0 years (range, 38-78). Across the cohorts, more than half of patients were male. In the weekly, biweekly, and prior TCR cohorts, 23.1%, 25.5%, and 31.4% of patients, respectively, had at least 1 extramedullary plasmacytoma; 31.1%, 28.9%, and 40.9% of patients, respectively, had high-risk cytogenetics.

The median prior lines of therapy in the weekly and biweekly cohorts were 5, with a range of 2 to 17 lines; in the prior TCR cohort, the median prior lines of treatment was 6 (range, 3-15). All patients had triple-class exposure status. Notably, 73.4%, 69.7%, and 78.4% of patients in the weekly, biweekly, and prior TCR cohorts, respectively, had penta-drug exposure.

Additional data presented at the 2023 ASCO Annual Meeting showed that the median DOR in the weekly cohort was 9.5 months (95% CI, 6.7-13.3); this was not reached (95% CI, 13.0-not evaluable [NE]) in the biweekly cohort and 11.9 months (95% CI, 4.8-NE) in the prior TCR cohort. Moreover, the 12-month DOR rates were 78.9%, 90.5%, and 80.5% of patients with a CR or better, respectively.

In the weekly, biweekly, and prior TCR cohorts, the 12-month PFS rates were 34.9%, 54.4%, and 38.1%, respectively; the 12-month OS rates were 76.4%, 77.4%, and 62.9%, respectively.

Regarding safety, the most frequent toxicities included cytokine release syndrome, dysgeusia, skin-related adverse effects (AEs), and nail-related AEs.

Moreover, 14.7% of those who received the weekly dose experienced AEs that required dose reductions; these rates were 8.3% and 9.8% in the biweekly and prior TCR cohorts, respectively. A total of 5 patients discontinued treatment because of skin-related toxicities and dysgeusia. Immune effector cell–associated neurotoxicity syndrome was observed in 10.7% of those who received the weekly dose, 11.0% of those who received the biweekly dose, and 2.9% of those who had prior TCR.

Grade 3 or 4 infections occurred in 19.6% of those in the weekly cohort, 14.5% of those in the biweekly cohort, and 27.5% of those in the prior TCR cohort. Infections resulted in discontinuation of study treatment for 1.4%, 0%, and 2.0% of patients, respectively. The incidence of opportunistic infections was reportedly low, at 3.5%, 5.5%, and 5.9%, respectively.

References

Janssen receives positive CHMP opinions for novel bispecific antibodies Talvey (talquetamab) and Tecvayli (teclistamab) for the treatment of patients with relapsed and refractory multiple myeloma. News release. Janssen Pharmaceutica NV. July 21, 2023. Accessed July 21, 2023. https://www.globenewswire.com/news-release/2023/07/21/2708857/0/en/Janssen-Receives-Positive-CHMP-Opinions-for-Novel-Bispecific-Antibodies-TALVEY-talquetamab-and-TECVAYLI-teclistamab-for-the-Treatment-of-Patients-with-Relapsed-and-Refractory-Multi.html
Schinke CD, Touzeau C, Minnema MC, et al. Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(suppl 16):8036. doi:10.1200/JCO.2023.41.16_suppl.8036