Teclistamab Snags Positive CHMP Opinion for Relapsed/Refractory Multiple Myeloma

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The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of a Type II variation for teclistamab in the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 3 prior therapies.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of a Type II variation for teclistamab in the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody and who have progressed on their last therapy.¹

The positive opinion for the reduced, biweekly dosing schedule is based on findings from the phase 1/2 MajesTEC-1 study (NCT03145181; NCT04557098).² Extended follow-up data showed that teclistamab elicited an overall response rate (ORR) of 63% in this patient population, with responses that deepened over time. At the time of the 2023 ASCO Annual Meeting presentation, over 45% of patients had received a complete response (CR) or better with the agent, and the median time to CR or better was 4.6 months (range, 1.6-18.5). Notably, the minimal residual disease (MRD) negativity rate by day 100 from the first dose of study drug was 81%.

The median duration of response (DOR) was 22 months (95% CI, 16-not estimable [NE]); this was extended in those who had a CR or better with the agent, at 27 months (95% CI, 22-NE). In all patients, the median progression-free survival (PFS) was 11 months (95% CI, 9-16); in those who achieved a CR or better, this was 27 months (95% CI, 23-NE). Lastly, the median overall survival (OS) was 22 months (95% CI, 15-NE) and NR in all patients and in those who achieved a CR or better, respectively.

“Pending approval, this variation for teclistamab will be an important step forward for this first BCMA bispecific therapy, offering flexible, less frequent dosing depending on a patient’s response,” Sen Zhuang, MD, PhD, vice president of Clinical Research and Development, Janssen Research & Development, ILLC, stated in a press release.¹

MajesTEC-1 enrolled patients with relapsed/refractory multiple myeloma who were triple-class exposed to a PI, IMiD, and an anti-CD38 monoclonal antibody. Patients needed to have an ECOG performance status of 0 or 1. They could not have previously received a BCMA-targeted therapy.³ The primary end point of the trial was ORR, and important secondary end points included pharmacokinetics/pharmacodynamics, DOR, PFS, OS, MRD negativity, safety, and health-related quality of life.

In another analysis of the trial, investigators evaluated the durability of responses in patients who switched from the weekly dose of the agent to the biweekly (Q2W) or monthly (Q4W) doses on the trial.

As of January 2023, a total of 165 patients were given teclistamab at the recommended phase 2 dose; 104 of these patients responded to treatment. Among the responders, 63 switched to Q2W dosing and 9 switched to Q4W dosing.

Data indicated that at the time of the switch, 85.7% of patients achieved a CR or better, 12.7% had a very good partial response, and 1.6% experienced a partial response.²

The median time to switch from QW to Q2W dosing was 11.3 months (range, 3-30). The median DOR was not yet reached at a median follow-up of 12.6 months (range, 1-25) since dosing switch. Notably, more than half of patients (68.7%; 95% CI, 53.6%-79.7%) who switched to a different dose approach continued to respond to teclistamab for 2 or more years since time of initial response. The majority (n = 42) of the 63 responders continued to respond after switching to less frequent dosing.

Regarding safety, it was reported that those who switched to Q2W or Q4W dosing experienced a lower incidence of grade 3 or higher infections than those who continued to receive the agent on QW dosing; these infection rates were 15.6% and 33.3%, 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
Janssen presents longer-term data for Tecvayli (teclistamab) showing a duration of response of 22 months in patients with relapsed or refractory multiple myeloma. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. June 5, 2023. Accessed July 21, 2023. https://www.janssen.com/emea/sites/www_janssen_com_emea/files/teclistamab_majestec-1_asco_2023_press_release.pdf
Usmani SZ, Karlin L, Benboubker L, et al. Durability of responses with biweekly dosing of teclistamab in patients with relapsed/refractory multiple myeloma achieving a clinical response in the majesTEC-1 study. J Clin Oncol. 2023;41(suppl 16):8034. doi:10.1200/JCO.2023.41.16_suppl.8034