CHMP recommendation would offer a GPRC5D-targeting bispecific antibody treatment option as early as the second line of therapy, if approved by the European Commission.
 

On Friday, October 16, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended extending the indication for Johnson & Johnson’s TALVEY® (talquetamab) in combination with daratumumab, with or without pomalidomide, to treat adults with relapsed/refractory multiple myeloma (RRMM) who have received at least one prior line of therapy, stated Johnson & Johnson in a press release.

If approved by the European Commission, the combination would offer a GPRC5D-targeting bispecific antibody treatment option as early as the second line of therapy. Talquetamab is currently authorized in the European Union as a single-agent treatment for eligible patients who have received at least three prior therapies and meet additional treatment-history criteria.

The CHMP recommendation is based on results from the ongoing Phase 3 MonumenTAL-3 trial (NCT05455320), which demonstrated significant improvements in progression-free survival (PFS), response rates and overall survival (OS) with talquetamab-based combinations compared with daratumumab, pomalidomide and dexamethasone (DPd).

Clinical trial results

At a median follow-up of 24.6 months, both talquetamab plus daratumumab (Tal-D) and talquetamab plus daratumumab and pomalidomide (Tal-DP) significantly improved PFS compared with DPd.

At 24 months:

• Progression-free survival: 81.3% with Tal-DP and 77.6% with Tal-D.
• Overall survival: 89.2% with Tal-DP, 87.9% with Tal-D and 83.0% with DPd.
• Overall response rate: 88.2% with Tal-DP, 88.5% with Tal-D and 77.6% with DPd.
• Complete response or better: 71.1% with Tal-DP, 68.9% with Tal-D and 34.5% with DPd.
• Minimal residual disease (MRD)-negative complete response or better: 52.3% with Tal-DP, 46.3% with Tal-D and 15.9% with DPd.

The PFS hazard ratio was 0.28 for Tal-DP (95% confidence interval [CI], 0.20–0.40; p<0.0001) and 0.33 for Tal-D (95% CI, 0.24–0.46; p<0.0001). These results correspond to approximately 72% and 67% lower relative hazards of disease progression or death, respectively, compared with DPd during the study follow-up.

OS also improved significantly. The hazard ratio was 0.47 for Tal-DP (95% CI, 0.30–0.73; p=0.0006) and 0.51 for Tal-D (95% CI, 0.33–0.78; p=0.0015), corresponding to approximately 53% and 49% lower relative hazards of death, respectively, compared with DPd. These relative hazard reductions are not equivalent to absolute reductions in the probability of death.

The trial enrolled 864 patients, all of whom had previously received lenalidomide and a proteasome inhibitor and had undergone at least one prior line of therapy. Most participants were refractory to lenalidomide (85.1%) and to their most recent treatment regimen (93.4%).

Safety findings

The overall safety profiles of the talquetamab combinations were consistent with the known safety profiles of the individual medicines. However, adverse events and infections were common across all three treatment groups.

Grade 3 or 4 treatment-emergent adverse events occurred in 94.9% of patients receiving Tal-DP, 74.8% receiving Tal-D and 91.5% receiving DPd.

Infections of any grade occurred in 87.3% of patients receiving Tal-DP, 84.3% receiving Tal-D and 83.0% receiving DPd. More severe infections, classified as grade 3 or 4, occurred in 37.7%, 29.2%, and 42.2% of patients, respectively.

Grade 5 adverse events, meaning fatal adverse events, occurred in 1.8% of patients receiving Tal-DP, 4.0% receiving Tal-D and 4.6% receiving DPd. Fatal adverse events attributed to infections accounted for 0.7%, 1.5%, and 1.8%, respectively.

Adverse events led to treatment discontinuation in 10.5% of patients in the Tal-DP group, 8.0% in the Tal-D group and 6.7% in the DPd group. At the data cutoff, 70.3%, 69.7%, and 47.3% of patients, respectively, remained on their assigned study treatment.

How the combination works

Talquetamab is a bispecific T-cell-engaging antibody that binds to GPRC5D, a protein highly expressed on multiple myeloma cells, and CD3 on T cells. This enables it to direct T cells towards myeloma cells and promotes their destruction. GPRC5D is a distinct target from B-cell maturation antigen (BCMA), another target used in multiple myeloma treatment and is absent or expressed at low levels on normal B cells.

Daratumumab targets CD38, a protein expressed on multiple myeloma cells, and promotes their destruction through immune-mediated mechanisms. Combining talquetamab and daratumumab therefore targets myeloma through two distinct mechanisms. Pomalidomide, an immunomodulatory medicine, is included in the Tal-DP regimen but not in Tal-D.

Johnson & Johnson said the findings support evaluating talquetamab-based combinations earlier in the treatment pathway, including in patients whose disease has relapsed or become refractory after at least one prior line of therapy.

Background and regulatory status

Talquetamab received conditional marketing authorization from the European Commission in August 2023 as a single-agent treatment for adults with RRMM who had received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and whose disease had progressed on their last treatment.  

The US Food and Drug Administration (FDA) also approved talquetamab in August 2023 for eligible patients who had received at least four prior lines of therapy.

The CHMP recommendation is a step in the European regulatory process. It does not constitute final European Commission approval of the expanded indication.

MonumenTAL-3 is an ongoing Phase 3 study evaluating Tal-D and Tal-DP against DPd. Its primary endpoint is PFS, with secondary endpoints including overall response rate, complete response or better, MRD negativity, OS, and safety.

Clinical significance

The results suggest that talquetamab-based combinations can improve disease control and response depth in previously treated multiple myeloma. Their potential role earlier in treatment will depend on the final regulatory decision, the overall benefit–risk assessment, and individual patient factors. The high incidence of adverse events, including severe infections and other serious toxicities, remains an important consideration when assessing treatment suitability.

A Summary of Product Characteristics from the EMA is available online to provide a full list of adverse events and information on dosage and administration, contraindications, and other precautions when using Talvey (talquetamab).

“In line with the European Medicine Agency’s regulations for new medicines and those given conditional approval, talquetamab is subject to additional monitoring,” said Johnson & Johnson.

References:

CHMP recommends approval of Johnson & Johnson’s TALVEY®▼ (talquetamab) plus daratumumab in earlier line treatment of relapsed/refractory multiple myeloma. Johnson & Johnson press release. October 16, 2026.

Talvey (talquetamab) Summary of Product Characteristics. European Medicines Agency.