CC-92480-MM-002 A Phase 1/2, Multicenter, Open-label, Study to Determine the Recommended Dose and Regimen, and Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination with Standard Treatments in Subjects with Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)

Overview

Sponsor-declared trial summary

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

3 Sep 2019 → ongoing

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Celgene Corporation

External identifiers

EU CT number

2023-505219-19-00

EudraCT number

2018-004767-31

WHO UTN

U1111-1233-5619

ClinicalTrials.gov

NCT03989414

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Dose response, Pharmacokinetic

To determine the recommended dose and regimen, and evaluate the safety and preliminary efficacy of mezigdomide in combination with standard treatments in subjects with RRMM and NDMM.

Secondary objectives 1

1. Evaluate additional measures of efficacy (time-to-response, duration of response, very good partial response or better and complete response rates) of mezigdomide in combination with standard treatments in subjects with RRMM and NDMM.

Conditions and MedDRA coding

Relapsed or refractory multiple myeloma (RRMM) and newly diagnosed MM (NDMM)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
5. Females of childbearing potential (FCBP) must agree and adhere to all testing and contraception requirements in the mezigdomide Global Pregnancy Prevention Plan (PPP). Duration of contraception for FCBP must be in accordance with the mezigdomide Global PPP, or 7 months after the last dose of BTZ (for Cohorts A, D and G), 90 days after the last dose of DARA (for Cohorts B and E), 6 months after the last dose of CFZ or ELO (for Cohorts C and F and Cohorts H and J), or 5 months after the last dose of ISA (for Cohorts I and K), whichever is later.
6. Male subjects must agree and adhere to all requirements in the mezigdomide Global PPP. Duration of contraception for male subjects must be in accordance with the mezigdomide Global PPP, or 3 months after the last dose of DARA (for Cohorts B and E), CFZ (for Cohorts C and F), and ISA (for Cohorts I and K), 4 months after the last dose of BTZ (for Cohorts A, D and G), or 6 months after the last dose of elotuzumab, whichever is longer, even if the subject has undergone a successful vasectomy.
7. Male subjects must agree to refrain from donating sperm or semen in accordance with the mezigdomide Global PPP, or for at least 3 months after the last dose of DARA, CFZ, and ISA, 4 months after the last dose of BTZ, or 6 months after the last dose of elotuzumab, whichever is later. Females must refrain from egg cell (ova) donation in accordance with the mezigdomide Global PPP.
8. All subjects must agree to refrain from donating blood while on study treatment and for 28 days after the last dose of study treatment.
9. All male and female subjects must also follow all other requirements defined in the mezigdomide Global PPP.
10. Please refer to protocol (Sec 4.2) for additional inclusion criteria.

Exclusion criteria 20

1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Subject has any condition that confounds the ability to interpret data from the study.
4. Subject has any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) < 1,000/µL (for Phase 1 without growth factor support for ≥ 7 days [≥ 14 days for pegfilgrastim]) prior to screening complete blood count [CBC]) b. Platelet count: < 75,000/µL (it is not permissible to transfuse a subject to reach this level) c. Hemoglobin < 8 g/dL (< 4.9 mmol/L) d. Creatinine clearance (CrCl) < 45 mL/min (< 30 mL/min for Cohort G) e. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L) f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN g. Serum total bilirubin > 1.5 x ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome h. Prothrombin time (PT)/international normalized ratio (INR) > 1.5 x ULN or partial thromboplastin time (PTT) > 1.5 x ULN, (for subjects not receiving therapeutic anticoagulation).
5. Subject has peripheral neuropathy ≥ Grade 2.
6. Subject with gastrointestinal disease that may significantly alter the absorption of mezigdomide.
7. Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the following non-invasive malignancies: • Basal cell carcinoma of the skin • Squamous cell carcinoma of the skin • Carcinoma in situ of the cervix • Carcinoma in situ of the breast • Incidental histologic finding of prostate cancer or prostate cancer that is curative
8. Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or clinically significant amyloidosis.
9. Subject with known central nervous system (CNS) involvement with myeloma.
10. Subject has received immunosuppressive medication within the last 14 days of initiating study treatment. Please refer to protocol for exceptions to this criterion.
11. Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following: • Left ventricular ejection fraction (LVEF) < 45% as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan at Screening. • Complete left bundle branch, bifascicular block or other clinically significant abnormal electrocardiogram (ECG) finding at Screening • A prolongation of QT interval on Screening ECG as defined by repeated demonstration of a QTc interval > 470 milliseconds (msec) using Fridericia's QT correction formula; a history of or current risk factors for torsades de pointe (eg, heart failure, hypokalemia, or a family history of Long QT Syndrome); and concurrent administration of medications that prolong the QT/QTc interval • Congestive heart failure (New York Heart Association Class III or IV). • Myocardial infarction within 12 months prior to starting study treatment. • Unstable or poorly controlled angina pectoris, including the Prinzmetal variant of angina pectoris • History of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, pericardial disease or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
12. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.
13. Concurrent administration of strong CYP3A modulators; concurrent administration of proton-pump inhibitors ≤ 2 weeks prior to starting mezigdomide
14. Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study.
15. Subject is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis A or C.
16. Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide, BTZ (for Cohorts A, D and G), DARA (for Cohorts B and E), CFZ (for Cohorts C and F), ELO (for Cohorts H and J), ISA (for Cohorts I and K), or dexamethasone.
17. Subject has known or suspected hypersensitivity to the excipients contained in the formulation of CC-92480, BTZ (for Cohorts A, D and G), DARA (for Cohorts B and E), CFZ (for Cohorts C and F), ELO (for Cohorts H and J), ISA (for Cohorts I and K), or dexamethasone.
18. Contraindications to the standard treatment regimens, per local prescribing information.
19. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis.
20. Please refer to protocol (Sec 4.3) for additional exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Recommend Dose and Regimen: Review of dose-limiting toxicities (DLTs), safety, and if applicable, pharmacokinetics (PK), pharmacodynamics (Pd), and/or preliminary efficacy data by the Safety Review Committee (SRC).
2. Safety: Type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment.
3. Overall response rate (ORR): Best response ≥ partial response (PR), according to the International Myeloma Working Group (IMWG) Uniform Response Criteria.

Secondary endpoints 4

1. Time-to-response (TTR) Time from first dose to the first documentation of response (PR or greater)
2. Duration of response (DOR) Time from the first documentation of response (PR or greater) to the first documentation of progressive disease (PD) or death
3. Complete Response (CR) rate Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria
4. Very good partial response (VGPR) rate (Cohorts D and E) Percentage of subjects who achieved VGPR or better according to IMWG Uniform Response Criteria.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 12

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 6

Locations

6 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 43 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications