Johnson & Johnson Submits Prospectus Highlighting Pivotal Rationale for TCE+TCE Combination Therapy in Relapsed/Refractory Multiple Myeloma with Extramedullary Disease

Jun 18, 2025 09:41 CST Updated 09:41

Johnson & Johnson

Medical Device R&D and Manufacturer

The TCE craze first emerged in the field of hematological oncology. Johnson & Johnson may be the first company to initiate clinical research on the combination of two TCE molecules, with its Phase 2 RedirecTT-1 study.EvaluatedGPRC5D-Targeted Bispecific AntibodyTALVEY (talquetamab) and GPRC5D-Targeted Bispecific Antibody Tecvayli（teclistamab）In triple exposure (Proteasome Inhibitors [PI], Immunomodulators [IMiDs], CD38 Monoclonal Antibodies) The efficacy in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD).

Triple Exposure and MergeEMD's MM represents patient populations with high unmet clinical needs. EMD is the aggressive form of MM.TheManifestation refers to the dissemination of myeloma cells to other parts of the body (such as soft tissues and organs) forming tumors (plasmacytomas). Due to disease complexities like tumor heterogeneity, these patients typically face limited treatment options and poor prognosis, with existing standard therapies showing a low overall response rate (ORR) and a propensity for rapid recurrence. Real-world data from the LocoMMotion study indicates that in patients with relapsed/refractory multiple myeloma (RRMM) who were previously triple-exposed or double-refractory to PIs and IMiDs, current treatment regimens resulted in a median progression-free survival (PFS) of only 4.6 months, an ORR of just 29.8%, a median overall survival (OS) of 12.4 months, and a median duration of response (DOR) of only 7.4 months. Moreover, most patients did not experience clinically meaningful improvements in health-related quality of life.On average,RRMM patients with triple exposure and EMD have an ORR of less than 40% and an mPFS of less than 6 months.

Phase 2 RedirecTT-1 study enrolled 90 patients with RRMM and EMD who had received extensive prior treatment. Among them, 84.4% were triple-class refractory, 35.6% were penta-drug refractory, 20.0% had previously received BCMA CAR-T therapy, and 8.9% had received bispecific antibody therapy. The combination of Talquetamab and Teclistamab achieved78.9% High ORR(95% Confidence Interval [CI]: 69.0-86.8), more than half of the patients (54.4%) achieved complete remission or better.High response rates (ORR of 83.3% and 75.0%, respectively) were still observed in patients previously treated with BCMA CAR-T or anti-FcRH5 TCE.As of the data cutoff, the median follow-up was 13.4 months, with 66.2% of responders maintaining ongoing relief, demonstrating deep and durable responses. The combination therapy allowed 61.0% of patients to remain progression-free at one year, with 64.1% of patients sustaining relief (median duration of relief: 13.8 months), and 74.5% of patients surviving at one year, with the median overall survival not yet reached.

This result demonstrates the benefits of simultaneously targeting GPRC5D and BCMA, and also lays the groundwork for Johnson & Johnson's subsequent BCMA/GPRC5D/CD3 trispecific antibody JNJ-5322. JNJ-5322 has completed Phase I clinical trials, which similarly targeted heavily pretreated patients, showing results that...Patients who have not received BCMA or GPRC5D drug treatments achieved an ORR of 100%, and the ORR for all subjects was 86%.The data was also presented at this year's EGA conference. Currently, there is disclosed data on BCMA and GPRC5D-targeted trispecific antibodies and autologous CAR-T, and cross-comparisons show:JNJ-5322 is superior to the Mabworks molecule.

Dr. Yael Cohen, Director of the Myeloma Unit at Sourasky Medical Center in Tel Aviv, Israel, stated: The investigational combination regimen of talquetamab and teclistamab has demonstrated deep and durable responses in patients with relapsed/refractory multiple myeloma and is now also showing significant potential in extramedullary myeloma patients, for whom standard therapies often prove ineffective. By simultaneously targeting GPRC5D and BCMA, this approach may reduce target antigen-related escape, thereby achieving higher ORR and deeper responses. The RedirecTT-1 trial has demonstrated the robust efficacy of this innovative dual-target combination as a potential treatment option for this disease.

In terms of drug resistance, the Blood literature shows: bispecific antibodies targeting BCMA or GPRC5DThe response rate is approximately70%Drug resistance is mainly divided into primary resistance and acquired resistance: 1) Primary resistance:NamelyTCell exhaustion, persistent antigen stimulation may lead toTCell function exhaustion, affecting its ability to kill tumors; 2) Acquired resistance:That is, the loss or downregulation of antigen expression, tumor cells may lose or reduce the expression of target antigens on their surface, thereby evading recognition by bispecific antibodies.Targeting both GPRC5D and BCMA simultaneously may reduce target antigen-related escape.

From the perspective of target distribution, according toRoche in2023 ASHPublished research,GPRC5DAndBCMAAlmost occupied100%The expression, just the difference between which one is higher. At the same time, targetedBCMA and GPRC5D may benefit more MM patients.

BCMA orGPRC5D-targeted TCEs in MM already have commercialized products. Combining validated targets and integrating them into a single molecule, this1+1'sThe idea includes exploring the combination of two monoclonal antibodies in the autoimmune field to form a bispecific antibody molecule, as well as the combination of PD-(L)1 and anti-angiogenic agents in the oncology field.DespiteNot very successful but unexpectedly gained the popularity of dual antibodies. As for whether it's 1+1≥2, or1+1＞1，Now WatchAs long as safety holds up, the logic makes sense.