(PA-059) A Phase 2 Study Measuring MRD Negativity after Talquetamab and Teclistamab Consolidation in Sequence As Part of First Line Treatment in Transplant Eligible Multiple Myeloma Patients (TALTEC)

Increasing minimal residual disease (MRD) negativity and search for possibly cure remain the goals of research efforts in multiple myeloma (MM) treatment. This study will evaluate the efficacy and tolerability of talquetamab and teclistamab in sequence, as consolidation after first line standard induction treatment in newly diagnosed multiple myeloma (NDMM) patients.  

Methods:   

In this open-label, multicenter phase 2 study, we enroll 50 NDMM patients eligible for high-dose therapy. Patients are treated with 6 cycles of daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd) with stem cell collection. This is followed by 6 cycles of talquetamab and 6 cycles of teclistamab in sequence. In follow up phase participants may receive standard of care with autologous stem cell transplantation (ASCT) and lenalidomide maintenance or only lenalidomide maintenance. Treatment response is  assessed according to International Myeloma Working Group (IMWG) criteria. MRD is  evaluated by next generation sequencing (NGS) and [18F] fluorodeoxyglucose positron emission tomography computed tomography (FDG PET-CT) at protocol-defined timepoints. Participants’ health related quality of life (QoL) and general well-being are captured using three patient reported outcome measures: PRO-CTCAE, EORTC-QLQ-C30 and FACT-Cog.
Primary endpoint is to determine MRD negative complete response rate at a sensitivity level of 10^-6 measured by NGS and FDG PET-CT after talquetamab and teclistamab consolidation therapy. Key secondary endpoints are to evaluate the proportion of participants achieving MRD negativity (10^-6) after induction treatment, conversion from positive MRD to negative MRD (10^-6) after talquetamab consolidation, conversion from positive MRD to negative MRD (10^-6) after teclistamab consolidation, and sustained MRD negativity.
Exploratory endpoints are to describe migration, clonal expansion and functional transition of T-cells, epigenetic changes of T-cell exhaustion, methylation status of resistant MM cells, and detect proteomic signatures from MRD positive and MRD negative patients by mass-spectrometry.


Results:   

The TALTEC study opened in June 2024 and is currently enrolling the patients. 49 patients out of sample size of 50 patients were enrolled in the study as of 30-May-2025. Futher information about baseline characteristics will be provided in the presentation.

Conclusions:   

TALTEC is an important study to evaluate the potential of sequencing two first in class T -cell redirectors   talquetamab and teclistamab as consolidation after D-VRd induction as an alternative treatment option to high-dose melphalan and ASCT through improved MRD negativity.

The study is conducted by North Estonia Medical Centre Foundation and Nordic Myeloma Study Group in collaboration and with the financial support from Janssen Pharmaceutica NV, a member of the Johnson & Johnson group of companies and with additional funding from Central Norway Health Region (EU CT 2023-508212-38-00; ClinicalTrial.gov NCT06505369).