IBERDOMIDE (IBER) IN COMBINATION WITH DEXAMETHASONE (DEX) AND DARATUMUMAB (DARA), BORTEZOMIB (BORT), OR CARFILZOMIB (CFZ) IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)
Author(s): ,
Sagar Lonial
Affiliations:
Winship Cancer Institute, Emory University,Atlanta,United States
,
Paul G. Richardson
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Rakesh Popat
Affiliations:
NIHR UCLH Clinical Research Facility,University College London Hospitals NHS Foundation Trust,London,United Kingdom
,
Edward Stadtmauer
Affiliations:
University of Pennsylvania,Philadelphia,United States
,
Jeremy Larsen
Affiliations:
Mayo Clinic,Scottsdale,United States
,
Albert Oriol
Affiliations:
Institut de Recerca contra la Leucèmia Josep Carreras and Institut Català d’Oncologia, Hospital Germans Trias i Pujol,Badalona,Spain
,
Stefan Knop
Affiliations:
Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg,Würzburg,Germany
,
Sundar Jagannath
Affiliations:
The Mount Sinai Hospital,New York,United States
,
Gordon Cook
Affiliations:
Clinical Trials Research Unit,Leeds Institute of Clinical Trials Research, University of Leeds,Leeds,United Kingdom
,
Ashraf Z. Badros
Affiliations:
The University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center,Baltimore,United States
,
Paula Rodríguez Otero
Affiliations:
Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC,Pamplona,Spain
,
David S. Siegel
Affiliations:
Division of Multiple Myeloma,John Theurer Cancer Center, Hackensack University Medical Center,Hackensack,United States
,
Tuong Vi Nguyen
Affiliations:
Bristol Myers Squibb,Princeton,United States
,
Antonia Di Micco
Affiliations:
Celgene International Sàrl, a Bristol-Myers Squibb Company,Boudry,Switzerland
,
Alpesh Amin
Affiliations:
Bristol Myers Squibb,Princeton,United States
,
Min Chen
Affiliations:
Bristol Myers Squibb,Princeton,United States
,
Elisabeth Kueenburg
Affiliations:
Celgene International Sàrl, a Bristol-Myers Squibb Company,Boudry,Switzerland
Niels W.C.J. van de Donk
Affiliations:
Amsterdam University Medical Center, VU Amsterdam, Department of Hematology, Cancer Center Amsterdam,Amsterdam,Netherlands
EHA Library. Lonial S. 06/09/21; 324595; S187
Prof. Sagar Lonial
Prof. Sagar Lonial
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S187

Type: Oral Presentation

Session title: New diagnostic and therapeutic approaches in multiple myeloma and AL amyloidosis

Background
IBER is an oral, novel cereblon E3 ligase modulator (CELMoD) compound with marked synergistic tumoricidal and immune-stimulatory effects in combination with proteasome inhibitors (PIs) or anti-CD38 monoclonal antibodies, preclinically and clinically. CC-220-MM-001 (NCT02773030) is an ongoing phase 1/2 study evaluating the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, and preliminary efficacy of IBER with different treatment combinations in independent cohorts, in pts with RRMM.

Aims
To report results from the IBER+DARA+DEX (IberDd), IBER+BORT+DEX (IberVd), and IBER+CFZ+DEX (IberKd) cohorts of the CC-220-MM-001 study.

Methods
Eligible pts received ≥2 prior regimens in the IberDd and IberKd cohorts, and ≥1 prior regimen in the IberVd cohort, containing lenalidomide or pomalidomide, and a PI. All pts had progressed ≤60 days of their last MM therapy. Escalating oral doses of IBER were given on Day (D)1–21 of each 28-D cycle in the IberDd cohort and in the IberKd cohort with weekly CFZ, and on D1–14 of each 21-D cycle in the IberVd cohort. DEX was given weekly in all 3 cohorts.

Results
As of Dec 14, 2020, 34 pts had received IberDd, 24 pts IberVd, and 7 pts IberKd. Exposure to prior regimens was heterogeneous (Table), all pts were refractory to their last prior regimen, and median number of prior therapies was 4.0 (2–12), 5.5 (1–14), and 6.0 (2–8), with IberDd, IberVd, and IberKd, respectively. IBER doses ranged from 1.0mg to 1.6mg. Median follow-up was 3.9 (0.1–20.7), 5.5 (1.2–18.0), and 5.1 (3.5–15.7) months, 15 (44%), 9 (38%), and 3 (43%) pts continue on treatment, and median cycles received was 4.0 (1–21), 7.5 (1–24), and 5.0 (3–16) with IberDd, IberVd, and IberKd, respectively.

Most frequent hematologic grade (G) 3–4 treatment-emergent adverse events (TEAEs) were neutropenia (63%), anemia (28%), leukopenia (28%), and lymphopenia (25%) with IberDd, neutropenia (29%) and thrombocytopenia (25%) with IberVd, and lymphopenia (57%) and neutropenia (43%) with IberKd. In all cohorts, neutropenia was managed with G-CSF. One pt (IberDd; 1.2mg) had G4 neutropenic sepsis. Occurrence of G3–4 non-hematologic TEAEs was low in all 3 cohorts. There were 12 (38%), 8 (33%), and 3 (43%) pts with ≥1 IBER dose reduction, with IberDd, IberVd, and IberKd, respectively.


In the IberDd cohort, the overall response rate (ORR) was 41% (12/29 pts: 1 stringent complete response [sCR], 2 CRs, 2 very good partial responses [VGPRs], 7 partial responses [PRs]), the clinical benefit rate (CBR) was 52%, and disease control rate (DCR) was 86%. In the IberVd cohort, ORR was 58% (14/24 pts: 2 CRs, 5 VGPRs, 7 PRs), CBR was 67%, and DCR was 92%. Responses with IberDd and IberVd were observed in DARA- and BORT-refractory pts, respectively. In the IberKd cohort, ORR was 57% (4/7 pts: 1 sCR, 2 VGPRs, 1 PR), CBR was 57%, and DCR was 86%. Median time to response was 4.1 (4.0–12.0), 3.6 (3.0–13.1), and 4.1 (4.1–8.1) weeks, in the IberDd, IberVd, and IberKd cohorts, respectively. Median duration of response is 63.3 weeks in the IberVd cohort, and not reached in the IberDd and IberKd cohorts.


RP2D was determined at 1.6mg in the IberDd cohort, while dose evaluation continues in the IberVd and IberKd cohorts.


Updated data will be presented at the meeting.

Conclusion
In heavily pretreated pts with RRMM, IberDd, IberVd, and IberKd showed a manageable safety profile and promising efficacy including CRs, even among DARA- and BORT-refractory pts. The study is ongoing. These results support further development of IBER-based regimens in MM, including the initiation of phase 3 combination studies.

Keyword(s): Clinical trial, Immunomodulation, Multiple myeloma, Phase I/II

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S187

Type: Oral Presentation

Session title: New diagnostic and therapeutic approaches in multiple myeloma and AL amyloidosis

Background
IBER is an oral, novel cereblon E3 ligase modulator (CELMoD) compound with marked synergistic tumoricidal and immune-stimulatory effects in combination with proteasome inhibitors (PIs) or anti-CD38 monoclonal antibodies, preclinically and clinically. CC-220-MM-001 (NCT02773030) is an ongoing phase 1/2 study evaluating the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, and preliminary efficacy of IBER with different treatment combinations in independent cohorts, in pts with RRMM.

Aims
To report results from the IBER+DARA+DEX (IberDd), IBER+BORT+DEX (IberVd), and IBER+CFZ+DEX (IberKd) cohorts of the CC-220-MM-001 study.

Methods
Eligible pts received ≥2 prior regimens in the IberDd and IberKd cohorts, and ≥1 prior regimen in the IberVd cohort, containing lenalidomide or pomalidomide, and a PI. All pts had progressed ≤60 days of their last MM therapy. Escalating oral doses of IBER were given on Day (D)1–21 of each 28-D cycle in the IberDd cohort and in the IberKd cohort with weekly CFZ, and on D1–14 of each 21-D cycle in the IberVd cohort. DEX was given weekly in all 3 cohorts.

Results
As of Dec 14, 2020, 34 pts had received IberDd, 24 pts IberVd, and 7 pts IberKd. Exposure to prior regimens was heterogeneous (Table), all pts were refractory to their last prior regimen, and median number of prior therapies was 4.0 (2–12), 5.5 (1–14), and 6.0 (2–8), with IberDd, IberVd, and IberKd, respectively. IBER doses ranged from 1.0mg to 1.6mg. Median follow-up was 3.9 (0.1–20.7), 5.5 (1.2–18.0), and 5.1 (3.5–15.7) months, 15 (44%), 9 (38%), and 3 (43%) pts continue on treatment, and median cycles received was 4.0 (1–21), 7.5 (1–24), and 5.0 (3–16) with IberDd, IberVd, and IberKd, respectively.

Most frequent hematologic grade (G) 3–4 treatment-emergent adverse events (TEAEs) were neutropenia (63%), anemia (28%), leukopenia (28%), and lymphopenia (25%) with IberDd, neutropenia (29%) and thrombocytopenia (25%) with IberVd, and lymphopenia (57%) and neutropenia (43%) with IberKd. In all cohorts, neutropenia was managed with G-CSF. One pt (IberDd; 1.2mg) had G4 neutropenic sepsis. Occurrence of G3–4 non-hematologic TEAEs was low in all 3 cohorts. There were 12 (38%), 8 (33%), and 3 (43%) pts with ≥1 IBER dose reduction, with IberDd, IberVd, and IberKd, respectively.


In the IberDd cohort, the overall response rate (ORR) was 41% (12/29 pts: 1 stringent complete response [sCR], 2 CRs, 2 very good partial responses [VGPRs], 7 partial responses [PRs]), the clinical benefit rate (CBR) was 52%, and disease control rate (DCR) was 86%. In the IberVd cohort, ORR was 58% (14/24 pts: 2 CRs, 5 VGPRs, 7 PRs), CBR was 67%, and DCR was 92%. Responses with IberDd and IberVd were observed in DARA- and BORT-refractory pts, respectively. In the IberKd cohort, ORR was 57% (4/7 pts: 1 sCR, 2 VGPRs, 1 PR), CBR was 57%, and DCR was 86%. Median time to response was 4.1 (4.0–12.0), 3.6 (3.0–13.1), and 4.1 (4.1–8.1) weeks, in the IberDd, IberVd, and IberKd cohorts, respectively. Median duration of response is 63.3 weeks in the IberVd cohort, and not reached in the IberDd and IberKd cohorts.


RP2D was determined at 1.6mg in the IberDd cohort, while dose evaluation continues in the IberVd and IberKd cohorts.


Updated data will be presented at the meeting.

Conclusion
In heavily pretreated pts with RRMM, IberDd, IberVd, and IberKd showed a manageable safety profile and promising efficacy including CRs, even among DARA- and BORT-refractory pts. The study is ongoing. These results support further development of IBER-based regimens in MM, including the initiation of phase 3 combination studies.

Keyword(s): Clinical trial, Immunomodulation, Multiple myeloma, Phase I/II

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies