Teclistamab FDA Approval Sought to Treat Relapsed/Refractory Multiple Myeloma

An application for FDA approval has been filed for teclistamab as a potential treatment for patients with relapsed or refractory multiple myeloma.

A biologics license application has been submitted to the FDA for teclistamab as treatment of patients with relapsed or refractory multiple myeloma, the Janssen Pharmaceutical Companies of Johnson & Johnson announced in a press release.1

Teclistamab is a novel, off-the-shelf, T-cell redirecting, bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3. The agent redirects CD3-positive T-cells to BCMA-expressing myeloma cells, inducing tumor cell death. The BLA for teclistamab is supported by data from the MajesTEC-1 (NCT04557098, NCT03145181) study.

"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," said Peter Lebowitz, MD, PhD, global therapeutic area head, Oncology, Janssen Research & Development, LLC, in a press release. "We look forward to working with the FDA in their review of our teclistamab submission."

MajesTEC-1 is a phase 1/2, first-in-human, open-label, dose-escalation study of teclistamab for the treatment of patients with relapsed or refractory multiple myeloma. In the study, teclistamab achieved deep and durable responses with a manageable safety profile, according to updated findings recently presented during the American Society of Hematology Annual Meeting and Exposition 2021.2

The population treated in MajesTEC-1 had a median age 64.0 years (range, 33–84) with 15% of patients being ≥75. The cohort was also 59% male. The median number of prior lines of therapy among patients in the study was 5 (range, 2–15), and 100% were triple-class, 69% were penta-drug exposed, 77% were triple-class refractory, and 29% were penta-drug refractory.

At a median follow-up of 8.2 months (range 1.2–15.2), the overall response rate (ORR) was 65% (95% CI 48-79) among the 40 patients treated with the recommended phase 2 dose of 1500 µg/kg following step-up doses of 60 and 300 µg/kg of subcutaneous teclistamab. Responses observed with the investigational therapy include a ≥ very good partial response rate of 60% (95% CI 43–75), and a complete response rate of 40% (95%, CI 25-57).

Responses to teclistamab appeared to deepen over time. The median duration of response had not been reached by the data cutoff date of June 14, 2021. The 6-month DOR was 90% (95% CI 63-97).

Safety data showed that cytokine release syndrome (CRS) was the most common non-hematologic adverse event (AE). The most common hematologic AEs were neutropenia (53), anemia (41%), and thrombocytopenia (33%). Notably, 4 patients in the study developed immune effector cell-associated neurotoxicity syndrome.

The MajesTEC-1 study is ongoing globally. Several centers including those in Michigan, New York, China, and Italy are actively recruiting patients who have an ECOG performance status of 0 or 1 and measurable disease.3

"The deep expertise, creativity, and persistence of the entire Janssen R&D organization enabled the expeditious advancement of teclistamab for multiple myeloma," said Mathai Mammen, MD, PhD, global head, Janssen Research & Development, Johnson & Johnson, in the press release.1 "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 U.S. 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://prn.to/3ew4BGT

2. Moreau P, Usamani S, Garfall A, et al. 896 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: 63rd Annual American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 3938. Accessed December 14, 2021.

3. A study of teclistamab, in participants with relapsed or refractory multiple myeloma (MajesTEC-1). News release. Accessed December 29, 2021. https://bit.ly/32A8k3V