Johnson & Johnson: TALVEY plus DARZALEX FASPRO shows superior PFS and OS in Phase 3 MonumenTAL‑3
- MonumenTAL‑3: TALVEY plus DARZALEX FASPRO with/without pomalidomide reduced risk of progression or death by up to 72% versus DPd (Tal‑DP HR 0.28; Tal‑D HR 0.33).
- 24‑month PFS: 81.3% (Tal‑DP), 77.6% (Tal‑D) vs 51.2% (DPd); 24‑month OS: 89.2%, 87.9% vs 79.1%, respectively.
- All 864 patients had prior lenalidomide and a proteasome inhibitor; 85.1% were lenalidomide‑refractory and 11.8% had prior anti‑CD38 exposure.
- Johnson & Johnson has submitted a supplemental BLA to the FDA and a Type II variation to the EMA for the combination after ≥1 prior line of therapy.
Key results
At a median follow‑up of 24.6 months, MonumenTAL‑3 showed significant PFS benefit for Tal‑DP (HR 0.28; 95% CI 0.20–0.40; p<0.0001) and Tal‑D (HR 0.33; 95% CI 0.24–0.46; p<0.0001) versus DPd. Twenty‑four‑month PFS rates were 81.3% (Tal‑DP), 77.6% (Tal‑D) and 51.2% (DPd). ORR was 88.2%, 88.5% and 77.6%; ≥CR rates were 71.1%, 68.9% and 34.5%; MRD‑negative ≥CR (10⁻⁵ NGS) rates were 52.3%, 46.3% and 15.9%. OS HRs were 0.47 (Tal‑DP) and 0.51 (Tal‑D) with 24‑month OS rates of 89.2%, 87.9% and 79.1% (DPd).
Study population and context
MonumenTAL‑3 randomized 864 patients with relapsed/refractory multiple myeloma who had received at least one prior line including lenalidomide and a proteasome inhibitor. Most were refractory to lenalidomide (85.1%) and to their last line of therapy (93.4%); 11.8% had prior anti‑CD38 exposure. The primary endpoint was PFS; secondary endpoints included ORR, ≥CR, MRD‑negative ≥CR, OS and safety. Results were presented at EHA 2026 and published in The New England Journal of Medicine.
Safety
Grade 3/4 TEAE rates were 94.9% (Tal‑DP), 74.8% (Tal‑D) and 91.5% (DPd). Overall infection rates were 87.3%, 84.3% and 83.0%; Grade 3/4 infections were 37.7%, 29.2% and 42.2%, respectively. Grade 5 AEs occurred in 1.8% (Tal‑DP), 4% (Tal‑D) and 4.6% (DPd); discontinuations due to AEs were 10.5%, 8.0% and 6.7%. Cytokine release syndrome occurred in 67.8% (Tal‑DP) and 58.4% (Tal‑D), predominantly Grade 1–2; immune effector cell‑associated neurotoxicity syndrome was infrequent (2.9% and 1.8%) with no Grade ≥4 events. Taste changes, weight loss and ataxia/balance disorders were mostly low grade and rarely led to discontinuation.
Mechanism and regulatory pathway
TALVEY targets GPRC5D on myeloma cells and engages CD3 on T‑cells while largely sparing normal B‑cells. Based on these MonumenTAL‑3 data, Johnson & Johnson has submitted a supplemental biologics license application to the U.S. FDA and a Type II variation to the EMA seeking approval of TALVEY plus DARZALEX FASPRO with or without pomalidomide after at least one prior line of therapy.
Source: J&J
