Subcutaneous Bispecific Antibodies Are Effective in Pre-Treated Multiple Myeloma

Teclistamab and talquetamab, two investigational bispecific antibodies, showed promising responses for the treatment of pre-treated or relapsed multiple myeloma (MM) in phase 1 trials, according to data that will be presented at the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting.

Forty Percent Complete Response Rate with Teclistamab

Featured at ASCO 2021 are results from the phase 1 first-in-human dose escalation study of teclistamab, an investigational bispecific antibody targeting both B cell maturation antigen (BCMA) and CD3. This treatment was evaluated in 40 patients with relapsed/refractory MM (RRMM) with a median of five prior lines of therapy.

Patients received subcutaneous teclistamab 1500 μg/kg with a median follow-up of 7.1 months. All study participants were previously triple-class exposed to at least one proteasome inhibitor (PI), immunomodulatory drug (IMiD), and CD38 antibody, and 83% were triple-class refractory.

“We reported iniial findings for teclistamab at ASCO 2020, and study updates have observed a deepening of responses that have shown to be durable in a significant percentage of patients with RRMM,” said study investigator Amrita Y. Krishnan, MD, Director of the Judy and Bernard Briskin Center for Multiple Myeloma Research and Chief of the Division of Multiple Myeloma at City of Hope, via a press release.

The overall response rate (ORR) was 65%, with at least a very good partial response in 58% of patients. Forty percent of patients achieved a complete response. Median time to response was one month and median duration to response has not yet been reached. At follow-up, 85% of patients who responded (n = 22) are currently continuing treatment.

The investigators found no dose-limiting toxicities with this subcutaneous regimen. One patient reported grade 1 neurotoxicity. The most common adverse events (AEs) were cytokine release syndrome (CRS; 70%), and neutropenia (65%; grade ≥3, 40%).

“Teclistamab exposure was sustained across the dosing interval and exceeded target levels, and consistent T-cell activation was observed. With this latest follow-up data, we present further evidence of promising clinical activity in heavily pretreated patients, who are in urgent need of new therapeutic options,” said Dr. Krishnan.

GPRC5D-Targeted Treatment Spurs 70% Response Rate

Other phase 1 data being presented at ASCO 2021 includes a dose-escalation study of talquetamab, a novel antibody targeting both CD3 and GPRC5D. Thirty patients with RRMM received weekly subcutaneous talquetamab 405 μg/kg, with 10.0 and 60.0 μg/kg step-up doses during the first week of therapy. Patients had received a median of six prior lines of therapy, and 77% of patients were triple-class refractory to a PI, IMiD, and CD38 antibody. Eight patients (27%) received prior BCMA-targeted therapy.

After a median follow-up of 6.3 months, the ORR was 70%. Sixty-five percent of triple-class refractory patients (n = 15) and 83% of penta-drug refractory patients (n = 5) responded to talquetamab. At follow-up, median duration of response was not yet reached and 81% of patients who responded remained on treatment.

The most common adverse events were CRS (73%), neutropenia (67%; grade ≥3, 60%), anemia (57%; grade ≥3, 27%), and dysgeusia (60%). Infections occurred in 37% and neurotoxicity occurred in 7% of patients. More than three-quarters of patients (77%) experienced skin-related AEs. No dose-limiting toxicities occurred.

“We are encouraged that just six months after announcing the first talquetamab results at this dose, we already have follow-up data that suggest time to initial response is rapid (0.2–3.8 months) and a number of patient responses deepen with continuous therapy, supporting the further exploration of targeting both GPRC5D and CD3 in patients with MM,” said principal investigator Jesus G. Berdeja, MD, Director of Myeloma Research at the Sarah Cannon Research Institute, via a press release.

“As the only investigational bispecific antibody directed against the novel target GPRC5D, we are committed to fully exploring talquetamab, including new subcutaneous dosing strategies in MM,” said Sen Zhuang, MD, PhD, Vice President of Oncology Clinical Research at Janssen Research & Development, LLC.