Phase I-b study of isatuximab + carfilzomib in relapsed and refractory multiple myeloma (RRMM).
2018; Lippincott Williams & Wilkins; Volume: 36; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2018.36.15_suppl.8014
ISSN1527-7755
AutoresAjai Chari, Joshua Richter, Nina Shah, Sandy W. Wong, Sundar Jagannath, Hearn Jay Cho, Noa Biran, Jeffrey L. Wolf, Samir Parekh, Pamela N. Münster, Deepu Madduri, Frank Campana, Thomas G. Martin,
Tópico(s)Peptidase Inhibition and Analysis
Resumo8014 Background: Isatuximab (ISA) is an anti-CD38 mAb with potent anti-myeloma effects as monotherapy or together with lenalidomide (Len) + dexamethasone (d) in RRMM. Carfilzomib (K) is a proteasome inhibitor approved for use in RRMM as a single agent or in combination (Kd or LenKd). Objectives: The primary objective was to assess the maximum tolerated dose (MTD) of ISA + K in RRMM. Secondary objectives were assessment of safety, PK, immunogenicity, and efficacy (IMWG response criteria (ORR)). (NCT02332850) Methods: Eligible patients (pts) had disease progression after 2 prior lines, an ECOG < 3, and adequate organ function. A 3+3 dose escalation (DE) design was utilized. 3 dosing levels (DL) were tested: ISA 10 mg/kg Q2W, ISA 10 mg/kg QW x 4 then Q2W and ISA 20 mg/kg QW x 4 then Q2W in combination with K standard dose (27 mg/m2) and schedule. An expansion cohort (EC) of 18 pts was enrolled at DL2. Results: 15 pts were treated in DE and 18 in the EC. The median age (n = 33) was 61 yrs (range 39-79). Pts received a median of 3 (2-8) prior lines. All pts were IMid and PI exposed: 26/29 Len refractory (Refr), 21/29 Vel Refr, 13/29 Pom Refr and 8/11 K Refr. Median follow-up is 6.5m (0.5 – 24m). 29 pts are evaluable for response. ORR = 66% (1 sCR, 7 VGPR, 11 PR) and CBR is 86%. The median progression free survival has not been reached. Disposition: 15 pts have progressed (4 deaths from PD), 1 pt withdrew after 27 cycles and 17 remain on therapy. The median # of cycles given is 3 (range 1-27). No DLT or severe toxicity has been observed. Common adverse events (AEs-all grades, incidence ≥ 15%), were thrombocytopenia (66%), pain (60%), upper respiratory infection (56%), diarrhea (40%), fatigue (40%), anemia (33%), cough (33%), elevated creatinine (30%), nausea (30%), neutropenia (27%), headache (27%), dyspnea (16.7%) and fever (16.7%). Serious AEs occurred in 9pts and < 5% of AEs were Gr 3/4. Infusion reactions (IRs) were the most common ISA-related AE: 17 IRs in 16/32 pts (50%: Gr 1 (9) + Gr 2 (8)). Conclusions: Combining ISA and K appears safe; toxicity is c/w the AEs of the individual agents with few G3/4 AEs. Encouraging anti-MM activity (ORR 66%) was seen at all DLs. ISA 10 mg/Kg QW x 4 then Q2W dosing was selected for an ongoing Phase III trial of ISA + Kd versus Kd (IKEMA: NCT03275285). Clinical trial information: NCT-02332850.
Referência(s)