FDA Approval Sought for Teclistamab for Relapsed/Refractory Multiple Myeloma

A biologics license application seeking the approval of teclistamab for use in patients with relapsed or refractory multiple myeloma has been submitted to the FDA.

A biologics license application seeking the approval of the off-the-shelf, T-cell redirecting bispecific antibody, teclistamab (JNJ-64007957), for use in patients with relapsed or refractory multiple myeloma has been submitted to the FDA.1

The application is supported by findings from the phase 1/2 MajesTEC-1 trial (NCT04557098, NCT03145181), which showed that at a median follow-up of 7.8 months (range, 0.5-18), single-agent teclistamab elicited an objective response rate (ORR) of 62.0% (95% CI, 53.7%-69.8%) in this population.2

“Despite all the gains that have been made in treating multiple myeloma, the unmet need still remains very high. Our relentless pursuit of treatments for this disease continues with the same sense of urgency that we have always had,” Peter Lebowitz, MD, PhD, global therapeutic area head, Oncology, Janssen Research & Development, LLC, stated in a press release. “We look forward to working with the FDA in their review of our teclistamab submission.”

Although options have emerged for the treatment of triple-class exposed pateints with relapsed/refractory multiple myeloma, an unmet medical need still exists. Teclistamab was designed to bind to CD3 on T cells and BCMA on plasma cells to mediate T-cell activation and subsequent lysis of BCMA-expressing multiple myeloma cells.

For the first-in-human, open-label, multicohort, multicenter, dose-escalation MajesTEC-1 trial, investigators set out to examine the bispecific antibody in patients with relapsed or refractory multiple myeloma who previously received 3 or more lines of therapy and who were triple-class exposed.

To be eligible to enroll to cohort A of the trial, the triple-class–exposed cohort, patients needed to have measurable disease and have previously received a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. They could not have previously received a BCMA therapy.

In week 1 of treatment, participants were administered step-up doses of teclistamab subcutaneously at 0.06 mg/kg and 0.3 mg/kg. In cycles 1 and later, they received a weekly dose of the bispecific antibody at 1.5 mg/kg. Treatment was continued until disease progression.

The primary end point of the trial was ORR, and key secondary end points comprised duration of response (DOR), very good partial response (VGPR) or better, complete response (CR) or better, stringent complete response (sCR), time to response (TTR), minimal residual disease (MRD) status, progression-free survival (PFS), overall survival (OS), safety, pharmacokinetics, immunogenicity, and patient-reported outcomes.

In the phase 1 portion of the trial, investigators determined the recommended phase 2 dose for single-agent teclistamab to be 1.5 mg/kg, given weekly and subcutaneously, with step-up doses of 0.06 mg/kg and 0.3 mg/kg.

As of September 7, 2021, a total of 125 patients were included in the phase 2 1.5-mg/kg cohort. Fifty patients discontinued treatment because of disease progression (n = 29), death (n = 9), physician decision (n = 7), patient withdrawal (n = 4), or toxicity (n = 1). A total of 75 patients were still receiving treatment with the bispecific antibody.

The median treatment duration was 5.9 months (range, 0.2-18.0) for those included in the primary safety analysis. Moreover, 46.7% of patients received teclistamab for 6 months or longer, and 16.4% received it for 9 months or longer.

Among the 165 patients included in the safety analysis, the median age was 64.0 years (range, 33-84), and 14.5% of patients were aged 75 years or older. Moreover, 58.2% of patients were male, 81.2% were White, 11.3% had bone marrow plasma cells of 60% or higher, and 17.0% had 1 or more extramedullary plasmacytomas. Notably, 25.9% of patients had high-risk cytogenetics.

Regarding ISS stage, 52.5% of patients were stage I, 35.2% were stage II, and 12.3% were stage III. Additionally, 73.3% of patients had a baseline renal function of 60 mL/min/1.73 m2 or higher. The median time since diagnosis was 6.0 years (range, 0.8-22.7) and the median number of prior lines of therapy received was 5.0 (range, 2-14). The majority (81.8%) of patients previously underwent stem cell transplantation.

All patients were triple-class exposed, 70.3% were penta-drug exposed, and 3.6% of patients previously received selinexor (Xpovio). Additionally, 77.6% of patients were triple-class refractory, 30.3% were penta-drug refractory, and 89.7% were refractory to their last line of therapy.

Additional data presented during the 2021 ASH Annual Meeting showed that the CR rate was 7.3%, the CR or better rate with the bispecific antibody was 28.7%, the VGPR or better rate was 58.0%, and the sCR was 21.3%.

Moreover, the median time to first response in these patients was 1.2 months (range, 0.2-5.5), The MRD negativity rate was 24.7% (95% CI, 18.0%-32.4%) at a threshold of 10-5; this rate was 16.7% (95% CI, 11.1%-23.6%) at a threshold of 10-6. Notably, in those who achieved a CR or better, the MRD negativity rate was 41.9%.

At the time of clinical cutoff, the median follow-up for the 93 responders was 8.0 months (range, 2.4+ to 18.0), and 91.4% of responders had at least 6 months of follow-up. The median DOR had not yet been reached.

Responses proved to be durable and to deepen over time. At the time of data cutoff, 88.2% of responders were alive without the need for subsequent treatment or disease progression. Only 11 of 93 responders experienced progressive disease or death.

Additionally, the 6-month event-free rate for responders was 92.5% (95% CI, 80.6%-97.2%); the 9-month event-free rate was 85.9% (95% CI, 70.0%-93.7%). The 6- and 9-month PFS rates in these patients were 64.4% (95% CI, 56.0%-71.7%) and 58.5% (95% CI, 48.8%-67.0%), respectively.

The median OS had not yet been reached.

Teclistamab was found to be well tolerated with no patients requiring a dose reduction. Only 1 patient stopped treatment because of a toxicity and that patient experienced adenoviral pneumonia.

Moreover, 53.3% of patients experienced serious adverse effects (AEs) and serious AEs determined to be related to the bispecific antibody were reported in 33 patients. Additionally, 35.2% of patients experienced injection-site reactions and all were grade 1 or 2 in severity. Sixty-three percent of patients reported infections, 35.2% of which were grade 3 or 4. Opportunistic infections were observed in 5.5% of patients.

Additionally, 72.1% of patients had evidence of hypogammaglobulinemia. Nine deaths because of toxicities were reported although none were determined to be associated with teclistamab; these were due to COVID-19 (n = 7), pneumonia (n = 1), and hemoperitoneum (n = 1).

Cytokine release syndrome (CRS) was reported in 71.5% of patients, and 32.7% of patients experienced 2 or more CRS events. The median time to onset was 2 days (range, 1-6) and the median duration was 2 days (range, 1-9). Moreover, 66.1% of patients received supportive care measures, which could have included tocilizumab (Actemra; 36.4%), low-flow oxygen by nasal cannula (12.7%), steroids (7.9%), and single vasopressor (0.6%).

All CRS events were grade 1 or 2 in severity with the exception of 1 transient grade 3 CRS event that fully resolved. Ninety-seven percents of these events were confined to step-up and cycle 1 of treatment. All CRS events resolved with no treatment discontinuations related to this effect.

The overall incidence of neurotoxicity was low, with only 12.7% of patients experiencing this effect with the bispecific antibody. The most frequently reported neurotoxicity event was headache, which was experienced by 8.5% of patients.

“The deep expertise, creativity and persistence of the entire Janssen R&D organization enabled the expeditious advancement of teclistamab for multiple myeloma,” Mathai Mammen, MD, PhD, global head, Janssen Research & Development, Johnson & Johnson, stated in a press release. “Today’s submission is another important step in our commitment to bring to patients truly transformational medicines that profoundly impact their health.”


  1. Janssen submits biologics license application to US FDA seeking approval of teclistamab for the treatment of patients with relapsed or refractory multiple myeloma. News release. December 29, 2021. Accessed December 29, 2021. https://bit.ly/3FFmcYY
  2. Moreau P, Usmani SZ, Garfall A, et al. Updated results from MajesTEC-1: phase 1/2 study of teclistamab, a B-Cell Maturation Antigen x CD3 bispecific antibody, in relapsed/refractory multiple myeloma. Presented at: 2021 ASH Annual Meeting; December 13, 2021; Atlanta, GA. Abstract 896.