eligibility_summary
G1 (maintenance): ASCT ≤180 d pre‑enroll, start 60–180 d after, MRD+ (10^-5), no progression, ≤2 pre‑ASCT regimens, no prior allo/solid transplant, tox ≤G1. G2 (RRMM doublets): measurable disease, ≥3 prior lines incl PI, IMiD, anti‑CD38 or triple‑refractory. G3 (RRMM triplets): 1–3 lines incl PI+IMiD, not refractory, anti‑CD38 FEV1≥50%. All: ECOG 0–2, adequate organs. Exclude: other trials, prior modakafusp, CNS MM, active HBV/HIV/HCV, strong CYP3A4 inducers, steroids >10 mg, QTcF>480 ms.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1b study testing IV modakafusp alfa (TAK-573) in combinations for multiple myeloma. Modakafusp alfa is an antibody–cytokine fusion (immunocytokine): an anti-CD38 IgG linked to attenuated IFN-α2b that binds CD38+ myeloma/immune cells and delivers IFN to activate IFNAR/type I interferon signaling, driving direct antitumor effects and immune activation. Combinations and mechanisms: lenalidomide or pomalidomide (IMiDs) bind cereblon, degrade IKZF1/3, enhance T/NK cell activity, bortezomib (reversible proteasome inhibitor) and carfilzomib (irreversible PI) block the 26S proteasome, causing proteotoxic stress and apoptosis, daratumumab (anti-CD38 monoclonal antibody) induces ADCC/CDC/ADCP and depletes CD38+ immunosuppressive cells. Targets/pathways: CD38-expressing malignant plasma cells, IFNAR/type I IFN signaling, ubiquitin–proteasome system, and CRBN–IKZF axis, engaging NK/T effector functions.