Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - Other
Status
Ongoing, recruiting
Participants planned
260
Countries
2
Sites
4
Relapsed or Refractory Multiple Myeloma (RRMM)
To determine the safety and tolerability of CC-92480 and dexamethasone in combination with tazemetostat, BMS-986158, or trametinib in participants with RRMM. To define the RP2D and schedule of each combination in participants with RRMM.
Key facts
- Sponsor
- Celgene Corp.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 30 Dec 2022 → ongoing
- Decision date (initial)
- 2024-05-22
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2023-509384-25-00
- EudraCT number
- 2021-005167-51
- WHO UTN
- U1111-1269-5704
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Dose response, Efficacy, Safety, Therapy, Pharmacokinetic
To determine the safety and tolerability of CC-92480 and dexamethasone in combination with tazemetostat, BMS-986158, or trametinib in participants with RRMM.
To define the RP2D and schedule of each combination in participants with RRMM.
Secondary objectives 2
- To evaluate the preliminary efficacy of CC-92480 in novel combinations compared against control (CC-92480 + dexamethasone) in participants with RRMM.
- To characterize the pharmacokinetics of CC-92480 when administered in combination with tazemetostat, BMS-986158, or trametinib.
Conditions and MedDRA coding
Relapsed or Refractory Multiple Myeloma (RRMM)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10067095 | Multiple myeloma progression | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Signed written informed consent prior to any study procedure.
- ≥ 18 years of age the time of signing the ICF.
- Relapsed or refractory multiple myeloma (MM) and must: a. have documented disease progression during or after their last myeloma therapy. b. For part I dose finding: Be refractory to, intolerant to, or not a candidate for available, established therapies known to provide clinical benefit in MM. For Part 2 Dose Expansion: Be refractory to or have relapsed after at least 2 prior lines of therapy that include an IMiD, a proteasome inhibitor, an anti-CD38 mAb, and a T-cell redirecting therapy (TRT, eg, a CAR-T or T-cell engaging bispecific treatment) unless the participant is not a candidate for TRT
- Must have measurable disease.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
- Agree to follow the CC-92480 Pregnancy Prevention Plan (PPP)
Exclusion criteria 9
- Known active or history of central nervous system (CNS) involvement of MM.
- COVID-19 vaccine within 14 days prior to C1D1
- Plasma cell leukemia; Waldenstrom's macroglobulinemia; polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome; or clinically significant light-chain amyloidosis.
- Impaired cardiac function or clinically significant cardiac disease.
- For Part 1: received prior therapy with CC-92480.
- For Part 2: received prior therapy with CC-92480, tazemetostat, BMS- 986158, or trametinib.
- Previously received allogeneic stem-cell transplant at any time or received autologous stem-cell transplant within 12 weeks of initiating study treatment
- Received any of the following within 14 days prior to initiating study treatment: a. Plasmapheresis b. Major surgery c. Radiation therapy other than local therapy for myeloma associated bone lesions d. Use of any systemic anti-myeloma drug therapy
- Used any investigational agents within 28 days or 5 half-lives (whichever is shorter) prior to initiating study treatment.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Safety : Type, frequency, seriousness, and severity of adverse events (AEs), and relationship of AEs to study treatment.
- Recommended Phase 2 Dose (RP2D): Establish the RP2D for CC-92480 in each novel treatment combination with dexamethasone.
Secondary endpoints 6
- Overall Response Rate (ORR) : Best response ≥ partial response (PR), according to the International Myeloma Working Group (IMWG) Uniform Response Criteria89
- Complete Response Rate (CRR): Percentage of participants who achieved ≥ complete response (CR), according to IMWG Uniform Response Criteria
- Very Good Partial Response Rate (VGPRR) : Percentage of participants who achieved ≥ VGPR, according to IMWG Response Criteria
- Progression-Free Survival (PFS) : Time from enrollment to the first documentation of progressive disease (PD) or death from any cause during study, whichever occurs earlier
- Time-to-Response (TTR) : Time from first dose to the first documentation of response (≥ PR)
- Duration of Response (DOR) : Time from the first documentation of response (≥ PR) to the first documentation of PD or death
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 10
PRD988426 · Product
- Active substance
- Dexamethasone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Authorised
- ATC code
- H02AB02 — DEXAMETHASONE
- Marketing authorisation
- 40153.00.00
- MA holder
- MIBE GMBH ARZNEIMITTEL
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD808393 · Product
- Active substance
- Dexamethasone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Authorised
- ATC code
- H02AB02 — DEXAMETHASONE
- Marketing authorisation
- 33652.00.00
- MA holder
- GALENPHARMA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD9757318 · Product
- Active substance
- Mezigdomide
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- CELGENE CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
PRD9757438 · Product
- Active substance
- Mezigdomide
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- CELGENE CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
PRD9852263 · Product
- Active substance
- Mezigdomide
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL
- Authorisation status
- Not Authorised
- MA holder
- CELGENE CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
PRD9757642 · Product
- Active substance
- Mezigdomide
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- CELGENE CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
PRD9757763 · Product
- Active substance
- Mezigdomide
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- CELGENE CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
PRD9757716 · Product
- Active substance
- Mezigdomide
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- CELGENE CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
2-3-35-DIMETHYLTRIAZOL-4-YL-5-S-OXAN-4-YLPHENYLMETHYLPYRIDO32-BINDOL-7-YLPROPAN-2-OL
PRD3825774 · Product
- Active substance
- 2-3-35-DIMETHYLTRIAZOL-4-YL-5-S-OXAN-4-YLPHENYLMETHYLPYRIDO32-BINDOL-7-YLPROPAN-2-OL
- Other product name
- BET-Inhibitor
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
PRD10498773 · Product
- Active substance
- 2-3-35-DIMETHYLTRIAZOL-4-YL-5-S-OXAN-4-YLPHENYLMETHYLPYRIDO32-BINDOL-7-YLPROPAN-2-OL
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL USE
- Authorisation status
- Not Authorised
- MA holder
- BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
Comparator 4
SUB178719 · Substance
- Active substance
- Tazemetostat
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Mekinist 2 mg film-coated tablets
PRD3045799 · Product
- Active substance
- Trametinib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Authorised
- ATC code
- L01EE01 — -
- Marketing authorisation
- EU/1/14/931/005
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Mekinist 0.5 mg film-coated tablets
PRD3045762 · Product
- Active substance
- Trametinib
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Authorised
- ATC code
- L01EE01 — -
- Marketing authorisation
- EU/1/14/931/001
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Dexamethason-ratiopharm® 4 mg Tabletten
PRD668856 · Product
- Active substance
- Dexamethasone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Authorisation status
- Authorised
- ATC code
- H02AB02 — DEXAMETHASONE
- Marketing authorisation
- 54668.00.00
- MA holder
- RATIOPHARM GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Celgene Corp.
- Sponsor organisation
- Celgene Corp.
- Address
- Route 206 And Province Line Road
- City
- Princeton
- Postcode
- 08543-4000
- Country
- United States
Scientific contact point
- Organisation
- Celgene Corp.
- Contact name
- GSM-CT
Public contact point
- Organisation
- Celgene Corp.
- Contact name
- GSM-CT
Third parties 11
| Organisation | City, country | Duties |
|---|---|---|
| Syneos Health Inc. ORG-100008382
|
Morrisville, United States | On site monitoring, Code 12, Code 2, Code 8, Code 9 |
| Frontage Laboratories Inc. ORG-100011515
|
Exton, United States | Other |
| Greenphire LLC ORG-100041621
|
King Of Prussia, United States | Other |
| QPS LLC ORG-100012847
|
Newark, United States | Other |
| Icon Clinical Research LLC ORG-100039864
|
Rochester, United States | Other |
| Hematogenix Laboratory Services Limited ORG-100047188
|
Cheadle, United Kingdom | Other |
| Azenta Germany GmbH ORG-100022621
|
Griesheim, Germany | Other |
| PPD Development LP ORG-100011560
|
Richmond, United States | Other |
| Cerba Research ORG-100042694
|
Gent, Belgium | Other |
| Azenta Germany GmbH ORG-100022621
|
Griesheim, Germany | Other |
| Q Squared Solutions Limited ORG-100042527
|
Livingston, United Kingdom | Other |
Locations
2 EU/EEA countries · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Norway | Ongoing, recruiting | 30 | 1 |
| Spain | Ongoing, recruiting | 26 | 3 |
| Rest of world
United Kingdom, United States, Canada
|
— | 204 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Norway | 2023-04-27 | 2023-04-27 | |||
| Spain | 2022-12-30 | 2022-12-30 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 26 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol Admin letter_2023-509384-25-00_redacted | 01 |
| Protocol (for publication) | D1_Protocol_EN_2023-509384-25-00_Redacted | 07 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_ESP | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_part 1_Redacted | 9.1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_part 2_Redacted | 3.1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PP_NO_Redacted | 1.4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Additional Research_Redacted | 4.4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Future Research_NO_Redacted | 1.3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_Part 1_Redacted | 9.1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_Part 2_Redacted | 3.1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner | 1.2.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material pregnancy prevention plan_ENG | 6.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material pregnancy prevention plan_NO | 8.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_PPP | 6.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_PPP information subject | 6.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Compare report_Tazemetostat RSI USPI | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Mekinist Trametinib_NSM_overview of changes_EMA | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Dexamethasone Aspen | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Dexamethasone Aspen_clarification | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Dexamethasone Aspen_clarification | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Tazemetostat Tazverik | NA |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Trametinib Mekinist | Rev 36 |
| Synopsis of the protocol (for publication) | D1_Protcol Synopsis_EN_2023-509384-25-00 | 02 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-509384-25_ES | 2.0 |
| Synopsis of the protocol (for publication) | D1_protocol synopsis_2023-509384-25_NO | 2.0 |
Application history
9 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-25 | Spain | Acceptable 2024-05-16
|
2024-05-16 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-07-22 | Spain | Acceptable 2024-09-23
|
2024-09-23 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-11-14 | Spain | Acceptable 2024-09-23
|
2024-11-14 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-03-07 | Spain | Acceptable 2025-05-07
|
2025-06-04 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-06-13 | Spain | Acceptable 2025-05-07
|
2025-06-13 |
| 6 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-07-31 | Spain | Acceptable 2025-09-05
|
2025-09-15 |
| 7 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-10-10 | Spain | Acceptable 2025-09-05
|
2025-10-10 |
| 8 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-12-04 | Spain | Acceptable 2026-01-27
|
2026-01-29 |
| 9 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2026-05-26 | Spain | Acceptable 2026-01-27
|
2026-05-26 |