Teclistamab/Daratumumab Combo Delivers Promising ORR in Heavily Pretreated Relapsed/Refractory Myeloma

Teclistamab (JNJ-64007957) in combination with daratumumab (Darzalex) produced intriguing preliminary efficacy data, including a promising overall response rate (ORR), in heavily pretreated patients with multiple myeloma, according to Paula Rodriguez-Otero, MD, PhD.

In findings from the phase 1b multicohort TRIMM-2 trial (NCT04108195), teclistamab and daratumumab improved ORR vs teclistamab alone, with ORR ranging between 70% and 100% across 3 different doses. The median follow-up was 5.1 months (range, 0.3-12.9), and the median time to first confirmed response was 1.0 month (range, 1.0-2.8).¹

“The combination of teclistamab and daratumumab with this preliminary efficacy suggests a promising ORR that could be even higher as compared [with] the efficacy of teclistamab as a single agent,” Rodriguez-Otero said.

In an interview with OncLive^®, Rodriguez-Otero, department of hematology, Clínica Universidad de Navarra, Pamplona, Spain, discussed the trial’s rationale, design, and findings assessing subcutaneous teclistamab in combination with daratumumab for the treatment of patients with relapsed/refractory multiple myeloma.

OncLive^®: Could you discuss the rationale and the background information on this study?

Rodriguez-Otero: This is a phase 1b multicohort study from the TRIMM-2 trial. In this particular cohort, we evaluated teclistamab subcutaneously in combination with daratumumab. The preclinical data showed that daratumumab, an anti-CD38 monoclonal antibody, may lead to synergistic clinical efficacy when combined to teclistamab, a bispecific antibody targeting BCMA.

[We have data] with daratumumab monotherapy leading to T-cell expansion and enhanced T-cell cytotoxic potential and preclinical studies showed that the addition of daratumumab may enhance the teclistamab mediated lysis of myeloma cells. This is the rationale behind the evaluation of this combination in this phase 1b clinical study.

Could you expand on the design of the study, including the methods and what patients were included?

Two different bispecific antibodies [were studied in this cohort]. In this case, we are speaking about teclistamab, which is a BCMA CD3 [T-cell redirecting bispecific antibody]. There is another cohort evaluating talquetamab, which is a GPRC5D-directed bispecific antibody. These 2 bispecific antibodies are evaluated in combination with daratumumab, and also in combination with daratumumab and pomalidomide.

In this particular abstract, we are seeing data of the combination of teclistamab and daratumumab. Patients were enrolled if they had received at least 3 prior lines of therapy or were double refractory to a proteasome inhibitor and an immunomodulatory drug. Treatment with [an] anti-CD38 monoclonal antibody was allowed, but there was a requirement for a 90-day washout period. Three different doses and schedules of teclistamab have been evaluated in combination with approved doses of subcutaneous [daratumumab].

Treatment was given until disease progression, and the key study objective for part 1 [was] to identify the recommended phase 2 dose for each treatment combination. For part 2, [the key objective] was to characterize the safety and overall antitumor activity of the different combinations.

What were the findings from the study?

A total of 37 patients have been included. Patients had heavily pretreated myeloma with a median of 5 prior lines of therapy. [Additionally], 76% of patients had been previously exposed to anti-CD38 monoclonal antibodies, 60% of the patients were also refractory to anti-CD38 monoclonal antibodies, and 54% of the patients were triple-class refractory.

The ORRs ranged from 70% to 100% on the different doses and schedules of teclistamab, with a high proportion of patients with deep responses, so very good partial responses, or better responses. Responses were quick in the first month and deepened over time, although the follow-up is still short for this study.

Regarding safety, teclistamab plus daratumumab was well-tolerated with no new adverse [effects] compared with the safety profile of the single drugs as previously reported.

Are there any next steps planned for this study? Do you see any future applications for this combination?

This study is aiming to evaluate the efficacy and the safety of the combination of the bispecific antibodies with other standards of care. [These preliminary data serve as] the basis of a phase 3 study [NCT05083169] that is a now ongoing that is called the MajesTEC-3 study. That is further evaluating the combination of teclistamab plus daratumumab in patients with relapsed/refractory multiple myeloma.

Reference

1. Rodriguez-Otero P, Dholaria B, Askari E, et al. Subcutaneous teclistamab in combination with daratumumab for the treatment of patients with relapsed/refractory multiple myeloma: results from a phase 1b multicohort study. Blood. 2021;138(suppl 1):1647. doi:10.1182/blood-2021-148723