MonumenTAL-3: trial | Bending the Curve: Trial by Trial

MonumenTAL-3

Talquetamab-Daratumumab in Relapsed or Refractory Myeloma (MonumenTAL-3)

Population

Relapsed or refractory multiple myeloma after at least one previous line of therapy.

Design

Phase 3 trial: 864 patients with at least one previous line of therapy were randomly assigned to talquetamab plus daratumumab and pomalidomide (Tal-DP), talquetamab plus daratumumab (Tal-D), or daratumumab plus pomalidomide and dexamethasone (DPd). The primary end point was progression-free survival assessed by an independent review committee; results are from an interim analysis.

Primary endpoint

PFS

Arms

Talquetamab + daratumumab + pomalidomide (experimental, n = 287): Talquetamab with daratumumab and pomalidomide
Talquetamab + daratumumab (experimental, n = 287): Talquetamab with daratumumab
DPd (control, n = 290): Daratumumab with pomalidomide and dexamethasone

People

Mina R

PFSHR 0.28 (95% CI 0.2–0.4)Δ 24-month PFS+30.1 pointsPFSHR 0.33 (95% CI 0.24–0.46)Δ 24-month PFS+26.4 pointsΔ ORR+10.6 pointsΔ ≥CR rate+36.6 points

Show the numbers

Results reported for MonumenTAL-3
Endpoint	Analysis	Talquetamab + daratumumab + pomalidomide / Talquetamab + daratumumab	DPd	Effect
PFSRandomised patients (864)	interimmedian follow-up 24.6 monthsMina 2026	81.3% at 2 y	51.2% at 2 y	HR 0.28 (95% CI 0.2–0.4)P<0.001
PFSRandomised patients (864)	interimmedian follow-up 24.6 monthsMina 2026	77.6% at 2 y	51.2% at 2 y	HR 0.33 (95% CI 0.24–0.46)P<0.001
ORRRandomised patients (864)	interimMina 2026	88.2%	77.6%	P<0.001P value as reported for the comparisons of each talquetamab group with DPd.
≥CR rateRandomised patients (864)	interimMina 2026	71.1%	34.5%	P<0.001
MRDRandomised patients (864)	interimMina 2026	52.3%	15.9%	P<0.001MRD-negative complete response.
OSRandomised patients (864)	interimmedian follow-up 24.6 monthsMina 2026	89.2% at 2 y	79.1% at 2 y	HR 0.47 (95% CI 0.30–0.73)
OSRandomised patients (864)	interimmedian follow-up 24.6 monthsMina 2026	87.9% at 2 y	79.1% at 2 y	HR 0.51 (95% CI 0.33–0.78)Serious adverse events occurred in 63.0%, 52.6% and 53.7% of the Tal-DP, Tal-D and DPd groups, respectively; fatal adverse events in 1.8%, 4.0% and 4.6%.

Results reported for MonumenTAL-3
Endpoint	Analysis	Talquetamab + daratumumab + pomalidomide / Talquetamab + daratumumab	DPd	Effect
PFSRandomised patients (864)	interimmedian follow-up 24.6 monthsMina 2026	81.3% at 2 y	51.2% at 2 y	HR 0.28 (95% CI 0.2–0.4)P<0.001
PFSRandomised patients (864)	interimmedian follow-up 24.6 monthsMina 2026	77.6% at 2 y	51.2% at 2 y	HR 0.33 (95% CI 0.24–0.46)P<0.001
ORRRandomised patients (864)	interimMina 2026	88.2%	77.6%	P<0.001P value as reported for the comparisons of each talquetamab group with DPd.
≥CR rateRandomised patients (864)	interimMina 2026	71.1%	34.5%	P<0.001
MRDRandomised patients (864)	interimMina 2026	52.3%	15.9%	P<0.001MRD-negative complete response.
OSRandomised patients (864)	interimmedian follow-up 24.6 monthsMina 2026	89.2% at 2 y	79.1% at 2 y	HR 0.47 (95% CI 0.30–0.73)
OSRandomised patients (864)	interimmedian follow-up 24.6 monthsMina 2026	87.9% at 2 y	79.1% at 2 y	HR 0.51 (95% CI 0.33–0.78)Serious adverse events occurred in 63.0%, 52.6% and 53.7% of the Tal-DP, Tal-D and DPd groups, respectively; fatal adverse events in 1.8%, 4.0% and 4.6%.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.28	0.2–0.4
PFS	0.33	0.24–0.46
OS	0.47	0.3–0.73
OS	0.51	0.33–0.78

Appears in

2025 Bispecifics move earlier: MajesTEC-3, MajesTEC-9, MonumenTAL-3

Sources

Mina R, Beksac M, Rodríguez-Otero P, Chen W, Mateos MV, Li J, et al. Talquetamab-Daratumumab in Relapsed or Refractory Myeloma. N Engl J Med. 2026;395(7):671-683.
PubMed DOI