Teclistamab Plus Darzalex Found to Ease Cancer Burden in Phase 1 Trial

Combo therapy works for patients with relapsed or hard-to-treat myeloma

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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teclistamab early trial results | Myeloma Research News | Illustration of bottle labeled clinical trials

A combination of the investigational therapy teclistamab and the approved medication Darzalex (daratumumab) reduced the cancer burden for most people with relapsed or refractory multiple myeloma (RRMM) in a clinical trial.

The patients in the study had received from two to 17 prior lines of therapy, with a median of six previous treatments, researchers noted.

“The preliminary results … showed tolerable safety with no overlapping toxicities, and encouraging efficacy, supporting the combination of teclistamab with [Darzalex] for the treatment of RRMM,” the team wrote.

These early findings were presented at the 2022 European Hematology Association (EHA) Annual Congress, in a talk titled “Teclistamab in Combination with Daratumumab, a Novel, Immunotherapy-based Approach for the Treatment of Relapsed/Refractory Multiple Myeloma: Updated Phase 1B Results.” The hybrid EHA Congress was held in person, in Vienna, Austria, and the virtual platform is open until Aug. 15.

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Teclistamab is a bispecific antibody, meaning it can bind to two different antigens — threats to the body’s immune system — at the same time. It is designed to bind to B-cell maturation antigen (BCMA), a protein expressed on myeloma cells, while simultaneously binding to CD3, a protein expressed by immune cells called T-cells.

The therapy is expected to prompt the T-cells to launch a powerful anti-cancer inflammatory attack.

Teclistamab in clinical trials

Teclistamab’s developer, Janssen, earlier this year applied for the therapy’s approval in the U.S. The company also sells Darzalex, an immunotherapy targeting the cancer protein CD38; it’s been approved for use in the U.S. since 2015.

Janssen is sponsoring the Phase 1 TRIMM-2 clinical trial (NCT04108195), which is testing teclistamab plus Darzalex in adults with RRMM who have received at least three prior lines of therapy. The study, launched in 2020, is still recruiting participants at sites in the U.S., Canada, and Europe.

Data presented at the EHA meeting covered 51 trial participants who had been followed for a median time of 8.6 months. Among the patients, 39 (76.5%) showed evidence of a response to treatment, after a median time of one month.

In all but three of the patients who responded, the response was graded as a “very good partial response” or better. The responses “remained durable and deepened over time,” according to Janssen.

“These data suggest the potential of a fully immune-based regimen for patients with heavily pretreated multiple myeloma,” Yusri Elsayed, MD, PhD, vice president, disease area leader, hematologic malignancies, at Janssen Research and Development, said in a press release.

“We are committed to the ongoing development of this combination and other treatments for patients who remain in need of new options,” Elsayed said.

The overall response rate was similar (73.7%) among participants who had previously been treated with a CD38-targeting medication.

“Responders to the combination of teclistamab plus subcutaneous [under-the-skin] daratumumab included patients with prior exposure to BCMA or anti-CD38 targeted agents, which is encouraging,” said Paula Rodríguez-Otero, MD, PhD, the trial’s principal investigator.

“These data also suggest this steroid-sparing regimen may lead to a clinically efficacious regimen in highly refractory patients,” said Rodríguez-Otero, from Clínica Universidad de Navarra in Spain.

Of the 39 patients who responded to the combination therapy, 26 were still alive and continuing in the trial at the time of data cut-off on Jan. 13, 2022, according to Janssen.

The most common adverse events (side effects) reported in the clinical trial so far have been an inflammatory condition called cytokine release syndrome (67.7%), low counts of immune cells called neutrophils (49.2%), and anemia (41.5%). One patient experienced immune effector cell–associated neurotoxicity syndrome (ICANS), an inflammation-associated neurological disorder, which was mild and fully resolved. No deaths during the study were related to treatment.

“Teclistamab in combination with [Darzalex] is a novel immunotherapy approach that may yield improved clinical efficacy in heavily pretreated patients with RRMM,” the researchers concluded.