European Commission Grants Conditional Marketing Authorization to Teclistamab for Multiple Myeloma

The European Commission has granted conditional marketing authorization to teclistamab (Tecvayli) for use as a single agent in adult patients with relapsed and 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.¹

The regulatory decision is supported by data from the phase 1/2 MajesTEC-1 trial (NCT03145181), which showed that at a median follow-up of 14.1 months (range, 0.3-24.4), the bispecific antibody elicited an objective response rate (ORR) of 63% (95% CI, 55.2%-70.4%) in this patient population (n = 104/165).² Among responders, 58.8% experienced a very good partial response (VGPR) or better and 39.4% achieved a complete response (CR) or better.

“The approval of teclistamab followed an accelerated approval pathway, supported via the European Medicines Agency’s PRIME scheme,” Edmond Chan, MBChB, MD, senior director and EMEA Therapeutic Area Lead of Hematology at Janssen-Cilag Limited, stated in a press release. “We would like to thank the medical community for recognizing the promise of teclistamab. Multiple myeloma is a complex disease that requires a complex set of solutions. Only by working together can we ensure that patients are able to benefit from innovation, such as teclistamab, as early as possible.”

Patients with a documented diagnosis of relapsed or refractory multiple myeloma who were at least 18 years of age were enrolled to the trial. Patients were required to have received at least 3 lines of prior therapy, including an IMiD, a PI, and an anti-CD38 antibody; they were also required to have progressive, measurable disease at the time of screening, and an ECOG performance status of 0 or 1.

Study participants were administered subcutaneous teclistamab at a dose of 1.5 mg/kg once weekly preceded by step-up doses of 0.06 mg/kg and 0.3 mg/kg. Notably, the step-up doses were separated by 2 to 4 days, and they were completed 2 to 4 days prior to the first full dose of teclistamab. For each of the step-up dose and the first full dose of the agent, patients were required to be hospitalized and were premedicated with 16 mg of dexamethasone, acetaminophen, and diphenhydramine.

Treatment was continued until progressive disease, intolerable toxicity, withdrawn consent, death, or study completion.

The primary end point of the phase 2 portion of the research was ORR per independent review committee assessment. Important secondary end points comprised duration of response, VGPR rate, CR or better rate, time to response, progression-free survival (PFS), and overall survival (OS). Other secondary end points included minimal residual disease status, safety, pharmacokinetics, and immunogenicity.

A total of 165 patients were enrolled to the trial; 40 patients were enrolled to the first phase of the trial and 125 were enrolled to the second phase. As of March 16, 2022, 42.4% of patients continued to receive teclistamab monotherapy, with a median duration of treatment of 8.5 months (range, 0.2-24.4).

Baseline characteristics were noted to be comparable in both phases of the trial. In the overall population, the median age was 64.0 years (range, 33.0-84.0), 58.2% were male, 81.2% were White, 66.7% had an ECOG performance status of at least 1, 52.5% had stage I disease, and the median number of prior lines of therapy received was 5, with a range of 2 to 14 lines.

Notably, all patients were triple-class exposed, and 70.3% were penta-drug exposed. Moreover, 92.1% of patients were refractory to an IMiD, 86.1% to a PI, and 89.7% to an anti-CD38 monoclonal antibody; 77.6% of patients were triple-class refractory, 30.3% were penta-drug refractory, and 89.7% were refractory to the last line of therapy that they received.

Additional data published in The New England Journal of Medicine showed that the median time to first response was 1.2 months (range, 0.2-5.5), and the median time to best response was 3.8 months (range, 1.1-16.8). Moreover, 26.7% of patients were MRD negative (95% CI, 20.1%-34.1%), and 46% of patients who achieved a CR or better did not have MRD.

Responses to teclistamab were noted to be lower in those with extramedullary disease, stage III disease, and who had at least 60% marrow replacement by plasma cells; these responses were higher in patients who did not receive more than 3 prior lines of treatment.

Notably, responses to the bispecific antibody deepened over time. The median DOR with teclistamab was 18.4 months (95% CI, 14.9–not estimable [NE]). The median PFS was 11.3 months (95% CI, 8.8-17.1), and the median OR was 18.3 months (95% CI, 15.1-NE)—although OS data were not mature following censoring of data for 97 patients.

The most frequently experienced toxicities with teclistamab included cytokine release syndrome (72%; grade 3, 0.6%), neutropenia (71%; grade 3 or 4, 64%), and anemia (55%; grade 3 or 4; 37%). Infections occurred frequently, the most common of which were upper respiratory tract infections (37%; grade 3 or 4, 2.4%) and pneumonia (28%; grade 3 or 4, 19%). Seventy-five percent of patients had hypogammaglobinemia occur, and 39% received immunoglobulin therapy.

References

1. 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. The Janssen Pharmaceutical Companies of Johnson & Johnson. August 24, 2022. Accessed August 24, 2022. https://bwnews.pr/3TgQzfi
2. Moreau P, Garfall AL, van de Donk NWC, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478