According to the results of the phase 1b MajesTEC-2 study, the immune-based triplet therapy regimen of teclistamab-cqyv, a first-in-class, BCMAxCD3 bispecific T-cell engager antibody, in combination with daratumumab and hyaluronidase-fihj and lenalidomidehad had a manageable safety profile with no unexpected safety signals observed.

A very good partial response (VGPR) or better was achieved by 90.3 percent of patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy, including a proteasome inhibitor and immunomodulatory drug, with responses deepening over time.

These data were presented during the 2022 American Society of Hematology (ASH) Annual Meeting (Abstract #160).

"These results show the potential of the combination of the bispecific BCMA-directed antibody teclistamab with the anti-CD38 antibody daratumumab and lenalidomide in the treatment of patients with relapsed or refractory multiple myeloma," said Emma Searle, M.D., Ph.D., Consultant Hematologist and Honorary Senior Lecturer, The Christie Hospital and University of Manchester, England, and study investigator.† "This is the first presentation of data from a teclistamab-based triplet regimen and we are eager to better understand how this combination may benefit patients through ongoing clinical studies."

At a median follow-up of 8.4 months (range, 1.1 to 12.9), the overall response rate (ORR) was 93.5 percent.

 Among all patients in the trial, VGPRs or better were achieved by 90.3 percent of patients, and 54.8 percent of patients achieved a complete response (CR) or better.1 Median time to response was one month, and responses deepened.

The median time to CR or better was three months (range, 1 to 10.4).1 At data cut-off, 80.6 percent of patients remained progression-free and on treatment.1 Responses deepened over time, and median duration of response had not been reached.

"Following the recent regulatory approvals of teclistamab-cqyv in the U.S. and EU, as well as its inclusion in the NCCN Clinical Practice Guidelines in Oncology as a recommended treatment option for certain patients with multiple myeloma, we are encouraged by its potential to improve outcomes in combination regimens and for earlier lines of treatment," said Sen Zhuang, M.D., Ph.D., Vice President, Clinical Research and Development, Janssen Research & Development, LLC.

"We remain committed to addressing the unmet needs of patients with multiple myeloma through off-the-shelf immunotherapies like teclistamab-cqyv and where we can bring together novel therapeutic approaches in the treatment of complex blood cancers."

The primary objective of this cohort of the MajesTEC-2 study (NCT04722146) was to understand if the immunomodulatory effects of daratumumab and lenalidomide could enhance the function of teclistamab-cqyv, resulting in enhanced antimyeloma activity in a broader population of patients.

The MajesTEC-7 study (NCT05552222) will examine the potential of this combination in patients newly diagnosed with multiple myeloma.

The most frequent haematological adverse events (AEs) observed in the study included neutropenia (84.4 percent any grade, 78.1 percent grade 3/4) and thrombocytopenia (25 percent any grade, 15.6 percent grade 3/4).1 The most frequent non-haematological AE was cytokine release syndrome (CRS) (81.3 percent, all grade 1/2); 97 percent of CRS events occurred during cycle 1.

Other common non-hsematological AEs included fatigue (46.9 percent any grade, 6.3 percent grade 3/4); diarrhoea (46.9 percent any grade, none grade 3/4); cough (40.6 percent any grade, 3.1 percent grade 3/4); COVID-19 (37.5 percent any grade, 12.5 percent grade 3/4); insomnia (37.5 percent any grade, 3.1 percent grade 3/4); hypophosphatemia (31.3 percent any grade, 6.3 percent grade 3/4); pyrexia (31.3 percent any grade, 3.1 percent grade 3/4); upper respiratory tract infection (31.3 percent any grade, none grade 3/4); increased alanine aminotransferase (ALT) (28.1 percent any grade, 9.4 percent grade 3/4) and pneumonia (25 percent any grade, 15.6 percent grade 3/4).

Two patients discontinued therapy due to an AE (COVID-19), considered to be unrelated to the study by investigator assessment. Infections were common among patients in the study and the majority were low grade (90.6 percent any grade, 37.5 percent grade 3/4).

New Data from the Phase 1/2 MajesTEC-1 Study Evaluating teclistamab-cqyv  in Relapsed or Refractory Multiple Myeloma Patients

New correlative analyses were also presented from the MajesTEC-1 study (NCT04557098). Data from these analyses may be used to help better understand baseline immune and tumour correlatives associated with outcomes in patients treated with teclistamab-cqyv.

The data were presented during an oral abstract session (Abstract #97). Additional pharmacokinetic data evaluating potential drug interactions with teclistamab-cqyv were presented during a separate poster session (Abstract #3228), as well as analyses of serum teclistamab-cqyv concentrations after intravenous and subcutaneous administration (Abstract #1911), to improve understanding of the clinical pharmacological profile of teclistamab-cqyv.

Source: Janssen