Patients who have been heavily pretreated for relapsed/refractory multiple myeloma participated in the phase 2 study of bispecific T cell redirection antibodies. The participants responded to treatment with a combination of daratumumab and talquetamab. Clinical trial data was recently reported by Ash Publications.
As confirmed in the trial, talquetamab, a newly discovered bispecific T cell redirection antibody, works against GPRC5D and has shown significant antitumor effects in patients who have been heavily pretreated for refractory or relapsed multiple myeloma.
About Bispecific T Cell Redirection Antibody
Bispecific T cell redirection antibodies are a new class of therapeutic agents that simultaneously bind to cells by way of CD3 and to tumor cell-specific antigens (TSA) resulting in T cell killing of tumor cells.
The latest data, presented at the ASCO 2023 Annual Meeting, reflect the results of the phase 1 TRIMM-2 study (NCT04108195) but does not identify dosage or patients who received CD38 agents and T-cell redirection therapy.
Enrolled patients had a median of five prior lines of therapy. A total of 75.4% had undergone anti-CD38 treatments while 63.1% were found to be resistant to anti-CD38 treatment. At a follow-up of 8.6 months, the ORR rate was 76.5%.
About Multiple Myeloma (MM)
MM is a malignant plasma cell disorder characterized by soft spots in the bone called osteolytic lesions. These lesions can be painful and can cause fractures or breaks. There is also an increased risk of renal failure.
The study is based on the assumption that daratumumab, when combined with teclistamab or talquetamab may provide improved clinical responses via multiple mechanisms when treating refractory or relapsed MM.
About the Study
The goal of the study is to determine whether the combined daratumumab will lead to improved clinical responses with or without pomalidomide in the treatment of MM and to evaluate the safety of daratumumab, with or without pomalidomide, which has been shown to directly inhibit myeloma cell growth. Pomalidomide is used when MM has worsened while the patient is receiving treatment or within sixty days of the last treatment.
The study is structured to evaluate the combination of daratumumab with talquetamab or teclistamab, and the preliminary antitumor activity of each combination.
About the Study
The study consists of a screening period, treatment period, and post-treatment follow-up that may be up to 16 weeks after the last dose.
Efficacy, safety, and the movement of drugs within the body (pharmacokinetics), biomarkers, and immunogenicity will be assessed at specified time points.
The safety of participants will be followed throughout the study by a team consisting of the sponsor’s study team and other participating investigators.
Bhagirathbhai Dholaria, at Vanderbilt University’s Medical Center, is the lead author of the study. Professor Dholaria presents data confirming that the T-Cell bispecific antibody talquetamab targeting GPRC5D plus daratumumab shows durable responses with MM patients.
The criteria for eligibility to enroll in the study required patients to have received a minimum of three prior therapies which included a proteasome inhibitor that eliminates excess protein. Additional requirements were not having received an immunomodulatory drug or were double refractory to both nor had they received CD38-directed therapy in 90 days or less.
The highest priorities for Part 1 and Part 2, aside from those listed, were to identify the recommended Phase 2 dose and safety at that level. Antitumor activity was also a factor.
At the one-year mark, the proportion of patients who were still in response was 80.9%. Proportionately 88.4% of those patients had received prior T-cell redirection therapy while 94.1% had switched to more infrequent dosing.
According to Dr. Dholaria, adverse events (AEs) were mostly rated low-grade. Sixteen percent of AEs caused dose reduction or discontinuations.
No cytokine release syndrome (CRS) or immune effector-cell associated neurotoxicity syndrome was comparable to talquetamab monotherapy. Specifically, no CRS leading to the discontinuation of treatment occurred.
The majority of patients, (95.4%) were administered antifungal, antibacterial, or antiviral prophylaxis.
Dr. Dholaria explained that the low rate of grade infections may have been the result of B cells being spared by the combination.
In conclusion, Dr. Dholaria believes that talquetamab is potentially a well-suited partner for two-week dosing regimens.