FDA Grants Accelerated Approval to Teclistamab for Relapsed/Refractory Multiple Myeloma

Based on positive responses from the phase 1/2 MajesTEC-1 trial, the FDA has granted approval for the use of teclistamab-cqyv in relapsed or refractory multiple myeloma.

The FDA has granted an accelerated approval to teclistamab-cqyv (Tecvayli) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1

Data from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098) support this approval as in the study, teclistamab demonstrated an objective response rate (ORR) of 61.8% (95% CI, 52.1%-70.9%).

At a median follow-up of 7.4 months, the estimated duration of response rate (DOR) for responders given teclistamab was 90.6% at 6 months (95% CI, 80.3%-95.7%) and 66.5% (95% CI, 38.8%-83.9%) at 9 months. The median DOR was not estimable (NE; 95% CI, 9.0-NE).

Teclistamab, a novel, off-the-shelf, T-cell redirecting, bispecific antibody, targets both B-cell maturation antigen (BCMA) and CD3. The agent works by redirecting CD3-positive T-cells to BCMA-expressing myeloma cells, inducing tumor cell death.

MajesTEC-1 is a single-arm, open-label, multicenter trial which enrolled 110 patients with relapsed or refractory multiple myeloma.2 All patients had received at least 3 prior treatments, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Further, those included were aged 18 years and older, had progressive, measurable disease at screening, and an ECOG score of 0 or 1. Previous treatment with a BCMA-targeted therapy was not allowed.

A weekly subcutaneous injection of teclistamab at a dose of 1.5 mg/kilogram of body weight was administered to the enrolled patients after receiving step-up doses of 0.06 mg and 0.3 mg/kg. In phase 1 of the trial, the cycle duration was 21 days while in phase 2, it was 28 days. Patients continued to receive teclistamab until the occurrence of disease progression, unacceptable toxicity, withdrawal of consent, death, or the end of the study.

Overall response defined as a partial response or better was the primary end point of the study. Secondary end points included DOR, the time until response, progression-free (PFS), and overall survival.

Among the 110 patients enrolled, the median age was 66 years (range, 33-82) and 16% of patients were 75 or older. A total of 56% of patients were male and 91% were White. The median number of prior lines of therapy among patients was 5 (range, 2–15), and 100% were triple-class, 69% were penta-drug exposed, 77% were triple-class refractory, and 30.3% were penta-drug refractory.

Between March 3, 2020, to August 13, 2021, 165 patients were enrolled between 35 sites in 9 countries and treated with teclistamab at the recommended phase 2 dose of 1.5 mg per kilogram. Among these patients, 40 were enrolled in the phase 1 portion of the study, and 125 were enrolled in phase 2.

A total of 70 patients (42.4%) continued to receive treatment as of March 16, 2022, with a median treatment duration of 8.5 months (range, 0.2-24.4). Then, 98 patients (59.4%) received at least 6 months of teclistamab treatment, and 79 patients (47.9%) received at least 9 months of treatment. Further, the median relative dose intensity for all treatment cycles, including step-up doses, was 93.7%.

Findings revealed that along with the ORR of 61.8%, 28.2% of patients achieved a complete response (CR) or better. The median time to first response was 1.2 months (range 0.2-5.5 months).

Regarding safety, each of the 165 patients reported having an adverse event (AE) and 156 patients (94.5%) had a grade 3 or 4 AE. The most frequent AEs included cytokine release syndrome (CRS; 72.1%), neutropenia (70.9%), anemia (52.1%), and thrombocytopenia (40.0%). CRS was grade 3 in 0.6% of patients. There was no grade 4 CRS, neutropenia was grade 3 or 4 in 64.2% of patients, anemia was grade 3 or 4 in 37.0%, and thrombocytopenia was grade 3 or 4 in 21.2%.

A total of 76.4% of patients had infections and those which were grade 3 or 4 occurred in 44.8%. Twenty-four patients (14.5%) reported having neurotoxic events, including immune effector cell–associated neurotoxicity syndrome in 5 patients (3.0%), all of which were grade 1 or 2. Further, 1 patient had a dose reduction during cycle 21 due to recurrent neutropenia, and 104 patients (63.0%) skipped a dose because of their AEs.

Two patients discontinued treatment with teclistamab due to AEs, including grade 3 adenoviral pneumonia and grade 4 progressive multifocal leukoencephalopathy.

Sixty-eight patients (41.2%) died, and most deaths (41) were attributed to progressive disease. There were 19 patients who died from AEs, including 12 deaths due to Covid-19, and 5 deaths considered to be related to teclistamab, including 1 who had discontinued teclistamab due to progressive multifocal leukoencephalopathy, 2 patients who had contracted Covid-19, 1 patient who had hepatic failure, and 1 patient who had streptococcal pneumonia.

References
  1. FDA approves teclistimab-cqyv for relapsed or refractory multiple myeloma. News release. FDA. October 25, 2022. Accessed October 25, 2022. https://bit.ly/3Nl4ajv
  2. A study of teclistimab, in participants with relapsed or refractory multiple myeloma (MajesTEC-1). Clinicaltrials.gov. Updated October 6, 2022. Accessed October 25, 2022. https://clinicaltrials.gov/ct2/show/NCT04557098