伊比利亚多胺联合地塞米松治疗复发难治性多发性骨髓瘤IbIIa期剂量递增研究

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Iberdomide + Dexamethasone in R/R Multiple Myeloma: Safety
TEAEs and Events of Interest, n (%)
Cycle 1 Grade 3
Iberdomide + Dexamethasone (N = 66)
Continue treatment until PD, unacceptable toxicity, withdrawal
Iberdomide: Days 1-21 of each 28-day cycle. Dose escalation: 0.3 mg, 0.45 mg, 0.6 mg, 0.75 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg DEX: 40 mg (for patients ≤ 75 yrs) or 20 mg (for patients > 75 yrs) on Days 1, 8, 15, 22 of each 28-day cycle
Dose Level, mg 0.3 0.45 0.6 0.75 0.9 1.0 1.1 1.2 1.3
Patients, n 10 3 3 3 13 13 wenku.baidu.com0 8 3
Dose-Limiting Toxicities --------
1 patient with grade 4 sepsis 1 patient with grade 3 pneumonia
cycles LEN, POM, PI, documented disease progression within 60 days
of last therapy (N = 66)
Phase I (Dose Escalation) Cohort A Iberdomide
Cohort B Iberdomide + DEX
ISS at study entry, n (%) Stage I Stage II Stage III
Iberdomide + DEX (N = 66) 34 (51.5) 65 (33-79)
21 (31.8) 39 (59.1)
6 (9.1)
7.4 (2.8-20.1)
30 (45.5) 18 (27.3) 17 (25.8)
LEN refractory, n (%)
POM refractory, n (%)
IMiD agent refractory, n (%)
Proteasome inhibitor refractory, n (%)
CD38 monoclonal antibody refractory, n (%)
Iberdomide (CC-220): novel small molecule inhibitor of cereblon E3 ligase modulator
‒ Binding to cereblon induces degradation of target proteins, including Ikaros and Aiolos[1]
Lonial. ASCO 2019. Abstr 8006.
Slide credit: clinicaloptions.com
Iberdomide + Dexamethasone in R/R Multiple Myeloma: Response
ORR 32.2% 2 (3.4)
100
80 CBR 49.2%
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Cohort E Iberdomide + DEX + DARA
Cohort F Iberdomide + DEX + BORT
Cohort G Iberdomide + DEX + CFZ
Phase II (RP2D)
Cohort C Iberdomide (RP2D)
Cohort D Iberdomide (RP2D) + DEX
All Cycles
Grade 4
All Grade
Grade 3
Anemia
10 (15.2)
0
24 (36.4)
15 (22.7)
Neutropenia
6 (9.1)
6 (9.1)
22 (33.3)
10 (15.2)
Febrile neutropenia
0
0
3 (4.5)
3 (4.5)
Thrombocytopenia
Characteristic
Median prior therapies, n (range) ASCT, n (%) LEN, n (%) POM, n (%) Proteasome inhibitor, n (%) CD38 monoclonal antibody, n (%)
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
2 (3.0)
3 (4.5)
9 (13.6)
3 (4.5)
Fatigue
0
0
20 (30.3)
0
Peripheral sensory neuropathy
0
0
3 (4.5)
1 (1.5)
Diarrhea
0
0
10 (15.2)
0
Constipation
0
0
7 (10.6)
0
Deep vein thrombosis
1. Matyskiela. J Med Chem. 2018;61:535. 2. Bjorklund. ASH 2016. Abstr 1591. 3. Amatangelo. Blood. 2018;132:Abstr 1935. 4. Lonial. ASCO 2019. Abstr 8006.
Iberdomide Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase Ib/IIa Dose Escalation Study
CCO Independent Conference Highlights*
of the 2019 ASCO Annual Meeting; May 31 - June 4, 2019; Chicago, Illinois
This activity is supported by educational grants from Amgen and Celgene Corporation.
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Iberdomide + Dexamethasone in R/R Multiple Myeloma: Baseline Characteristics
Characteristic
Male, n (%)
Median age, yrs (range)
ECOG PS, n (%) 0 1 2
Median time since diagnosis, yrs (range)
0
0
1 (1.5)
0
Pulmonary embolism
0
0
1 (1.5)
1 (1.5)
Infection Pneumonia*
7 (10.6) 2 (3.0)
1 (1.5) 0
31 (47.0) 9 (13.6)
15 (22.7) 8 (12.1)
*Includes pneumonia, influenzal pneumonia, streptococcal pneumonia, and parainfluenzae viral pneumonia.
60
17 (28.8) 10 (16.9)
DCR 84.7%
ORR 35.3% 1 (2.0)
‒ Binds cereblon with higher affinity (20 x) than lenalidomide and pomalidomide[1]
‒ In preclinical models, demonstrated direct antimyeloma and immunostimulatory activity[2]
‒ Demonstrated enhanced apoptosis and antibody-dependent cellular toxicity synergistically with bortezomib and daratumumab[3]
Current phase Ib/IIa dose-escalation study designed to identify MTD/RP2D of iberdomide alone or in combination with chemotherapy in patients with R/R multiple myeloma[4]
Primary endpoints: MTD, DLT, RP2D, efficacy
Secondary endpoints: safety, ORR, TTR, DoR, PK, PFS, OS
Lonial. ASCO 2019. Abstr 8006.
Slide credit: clinicaloptions.com
Slide credit: clinicaloptions.com
Iberdomide + Dexamethasone in R/R Multiple Myeloma: Study Design
Phase Ib/IIa openlabel study
Adults with R/R MM, ECOG PS 0-2, ≥ 2 prior therapies, including ≥ 2 consecutive
Iberdomide + Dexamethasone in R/R Multiple Myeloma: Background
Immunomodulatory agents are standard of care for patients with multiple myeloma, yet relapse and refractory disease are common
Iberdomide + DEX (N = 66)
5 (2-12) 52 (78.8) 66 (100) 45 (68.2) 66 (100) 49 (74.2)
50 (75.8)
37 (56.1)
57 (86.4)
44 (66.7)
47 (71.2)
Lonial. ASCO 2019. Abstr 8006.
Grade 4 1 (1.5) 9 (13.6)
0 5 (7.6)
0 0 0 0 0 0 2 (3.0) 0
Lonial. ASCO 2019. Abstr 8006.
Slide credit: clinicaloptions.com
Iberdomide + Dexamethasone in R/R Multiple Myeloma: Dose-Limiting Toxicities