Johnson & Johnson: CHMP recommends TALVEY plus daratumumab for earlier-line RRMM
- CHMP recommends extending talquetamab (TALVEY) to use with daratumumab, with or without pomalidomide, for adults with relapsed/refractory multiple myeloma after at least one prior therapy.
- MonumenTAL-3 (median follow-up 24.6 months) showed PFS HRs of 0.28 for Tal‑D‑P and 0.33 for Tal‑D versus DPd; 24‑month PFS rates were 81.3% (Tal‑D‑P) and 77.6% (Tal‑D).
- Response and depth: ORRs were 88.2% (Tal‑D‑P), 88.5% (Tal‑D) and 77.6% (DPd); ≥CR rates 71.1%, 68.9%, 34.5%; MRD‑negative ≥CR rates 52.3%, 46.3%, 15.9% respectively.
- Overall survival improved: OS HR 0.47 for Tal‑D‑P and 0.51 for Tal‑D vs DPd; safety profiles were consistent with known monotherapy profiles, with high infection rates but lower Grade 3/4 infections for Tal‑D (29.2%).
CHMP recommendation
The EMA Committee for Medicinal Products for Human Use (CHMP) has recommended approval of an indication extension for talquetamab (TALVEY) to be used in combination with daratumumab, with or without pomalidomide, for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior therapy.
Mechanism and rationale
Talquetamab is a bispecific T‑cell engager that binds GPRC5D on myeloma cells and CD3 on T cells; GPRC5D expression is independent of BCMA and low on normal B‑cells. Daratumumab targets CD38. The combination is presented as complementary, aiming for enhanced antitumour activity while largely sparing healthy B‑cells.
MonumenTAL‑3 efficacy
In the Phase 3 MonumenTAL‑3 trial (NCT05455320) at a median follow‑up of 24.6 months, talquetamab plus daratumumab with pomalidomide (Tal‑D‑P) and talquetamab plus daratumumab (Tal‑D) significantly improved progression‑free survival versus daratumumab+pomalidomide+dexamethasone (DPd): PFS HRs were 0.28 (Tal‑D‑P) and 0.33 (Tal‑D). Twenty‑four‑month PFS rates were 81.3% (Tal‑D‑P) and 77.6% (Tal‑D). ORRs were 88.2% and 88.5% versus 77.6%; ≥CR rates were 71.1% and 68.9% versus 34.5%; MRD‑negative ≥CR (10⁻⁵ NGS) rates were 52.3% and 46.3% versus 15.9%. Both Tal‑D‑P and Tal‑D showed clinically meaningful OS benefit (HR 0.47 and 0.51 vs DPd) and 24‑month OS rates ~89.2% and 87.9%.
Safety and exposure
Safety was consistent with known monotherapy profiles. Grade 3/4 TEAE rates were 94.9% (Tal‑D‑P), 74.8% (Tal‑D) and 91.5% (DPd). Overall infection rates were high across arms (≈83–87%), with Grade 3/4 infections lowest for Tal‑D (29.2%). Grade 5 AEs occurred across arms (fewest in Tal‑D‑P). Treatment discontinuations due to AEs were 10.5% (Tal‑D‑P), 8.0% (Tal‑D) and 6.7% (DPd); at cutoff 69–70% remained on Tal‑D‑containing regimens versus 47.3% on DPd.
Regulatory and study context
MonumenTAL‑3 is an ongoing Phase 3 study comparing talquetamab+daratumumab ± pomalidomide to DPd in RRMM after ≥1 prior line. Talquetamab previously received a conditional marketing authorisation in the EU in August 2023 and has been administered to over 11,000 patients worldwide to date.
Source: J&J