European Commission Approves Reduced Dosing of Teclistamab in Relapsed/Refractory Myeloma

The European Commission has approved a Type II variation application for teclistamab-cqyv (Tecvayli), providing the option for a reduced dosing frequency of 1.5 mg/kg every 2 weeks in patients with relapsed/refractory multiple myeloma who have achieved a complete response (CR) or better for a minimum of 6 months.¹

The regulatory decision was supported by data from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098). Updated data demonstrated that among 104 responders treated at the recommended phase 2 dose (RP2D) of teclistamab of 1.5 mg/kg per week, 63 patients switched to dosing once every 2 weeks. At the time of switch, 85.7% of patients achieved a CR or better, 12.7% had a very good partial response (VGPR), and 1.6% experienced a PR.

The median time to switch to biweekly dosing was 11.3 months (range, 3-30). At a median follow-up of 12.6 months (range, 1-25) following the switch, the median duration of response was not yet reached, and the rate of patients who remained in response for at least 2 years from the time of first response was 68.7% (95% CI, 53.6%-79.7%).

After 12 to 18 months of follow-up, responders who switched to biweekly dosing within 12 months experienced a lower rate of grade 3 or higher infections (15.6%) compared with those who remained on weekly dosing at 12 months (33.3%). At data cutoff, 65% of patients (n = 41) remained on treatment.

“Every patient’s experience with multiple myeloma is unique and requires a different treatment approach, tailored to their specific needs,” Niels van de Donk, MD, professor of hematology at Amsterdam University Medical Centers, stated in a news release. “With a decreased incidence of new onset grade 3 or higher infections, low discontinuation rates, and depth of responses maintained, this biweekly dosing option for teclistamab could provide substantial benefit for people living with multiple myeloma, potentially offering reduced time spent in hospital.”

In August 2022, the EC granted conditional marketing authorization to teclistamab for use as a single agent in adult patients with relapsed/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.²

In October 2022, the FDA granted accelerated approval to teclistamab for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 previous lines of therapy, including a PI, an iMID, and an anti-CD38 monoclonal antibody.³

Both approvals were supported by prior data from MajesTEC-1, which was a single-arm, open-label, multicohort, multicenter study that evaluated the safety and efficacy of teclistamab in adults with relapsed/refractory multiple myeloma who received 3 or more prior lines of therapy (n = 165).¹

Phase 1 included dose-escalation and -expansion portions to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of teclistamab. Phase 2 examined the efficacy of teclistamab at the RP2D of 1.5 mg/kg given subcutaneously once per week with a primary end point of overall response rate.

Enrolled patients received a median of 5 (range, 2-14) prior lines of therapy. Patients who had achieved a confirmed PR or better following 4 or more cycles of treatment in phase 1, or a confirmed CR or better for 6 months or longer in phase 2, were eligible for reduced dosing at 1.5 mg/kg given subcutaneously every 2 weeks until disease progression or unacceptable toxicity.

“Following the initial EC approval for teclistamab in August 2022, our research has remained focused on how we can continue to advance the use of teclistamab to better meet individual patient needs and improve patient experiences,” Edmond Chan, MBChB, MD, senior director, lead of EMEA Therapeutic Area in Hematology at Janssen-Cilag Limited, stated in a news release. “Today’s approval for teclistamab provides eligible patients, their caregivers and physicians an additional, more flexible weight-based option with less frequent dosing depending on a patient’s response.”

References

1. European Commission approves reduced dosing frequency for Janssen’s bispecific antibody Tecvayli (teclistamab). News release. Janssen. August 18, 2023. Accessed August 18, 2023. https://www.globenewswire.com/news-release/2023/08/18/2727746/0/en/European-Commission-Approves-Reduced-Dosing-Frequency-for-Janssen-s-Bispecific-Antibody-TECVAYLI-teclistamab.html
2. Janssen marks first approval worldwide for Tecvayli (teclistamab) with EC authorisation of first-in-class bispecific antibody for the treatment of patients with multiple myeloma. News release. Janssen. August 24, 2022. Accessed August 18, 2023. https://www.businesswire.com/news/home/20220822005274/en/Janssen-Marks-First-Approval-Worldwide-for-TECVAYLI
3. FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. News release. FDA. October 25, 2022. Accessed August 18, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma