MEZIGDOMIDE for Relapsed/refractory multiple myeloma

Inclusion criteria

• {"criterion_text":"- Signed Written Informed Consent\n- Male participants must: •\tPractice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant woman or a WCBPFCBP while participating in the study, during dose interruptions and for at least 90 days after the last dose of mezigdomide or carfilzomib, even if he has undergone a successful vasectomy\n- Male participants must agree to refrain from donating sperm while on study intervention, during dose interruptions, and for at least 90 days following last dose of mezigdomide or carfilzomib.\n- Women must agree to refrain from donating eggs while on study intervention and for at least 28 days after last dose of mezigdomide\n- Participants must agree to refrain from donating blood while on study intervention, during dose interruptions, and for at least 28 days following the last dose of study intervention\n- All male and female participants must follow all requirements defined in the Pregnancy Prevention Plan in Appendix 11 for mezigdomide\n- Adult patients (≥18 years old)\n- ECOG Performance Status score of 0, 1, or 2\n- Participant has documented diagnosis of multiple myeloma (MM) and measurable disease, defined as any of the following: \tM-protein ≥ 0.5 g/dL by serum protein electrophoresis (sPEP), or \tM-protein ≥ 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP) or, \tFor participants without measurable disease in sPEP or uPEP: serum free light chain (sFLC) levels > 100 mg/L (10 mg/dL) involved light chain and an abnormal κ/λ FLC ratio\n- Participant has received one or two prior line of anti-myeloma therapy. Note: One line can contain several phases (eg, induction, [with or without] hematopoietic stem cell transplant, (with or without) consolidation, and/or [with or without] maintenance therapy)\n- Participant must have received prior treatment with lenalidomide and an anti-CD38 monoclonal antibody.\n- Participant achieved minimal response [MR] or better to at least 1 prior anti-myeloma therapy\n- Participant must have documented disease progression during or after their last antimyeloma regimen\n- Women of childbearing potential (WOCBP) must \tHave 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy and must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. \tEither commit to true abstinence* from heterosexual contact or agree to use, and be able to comply with, 2 forms of contraception: one highly effective, and one additional effective (barrier) contraception without interruption, 28 days prior to starting study intervention, during treatment (including dose interruptions), and for at least 28 days after the last dose of mezigdomide, or 6 months after the last dose carfilzomib, whichever is longest"}

Exclusion criteria

• {"criterion_text":"- Participant that received >= 3 prior line of anti-myeloma therapy\n- Participant has received any Major surgery (as defined by the Investigator) within 28 days of initiating study intervention.\n- Participant has received any Radiation therapy, other than local palliative therapy, for myeloma-associated bone lesions within 14 days of initiating study intervention\n- Participant with known central nervous system (CNS) involvement with myeloma\n- Participant has Use of any systemic anti-myeloma drug therapy within 14 days of initiating study intervention\n- Participant has previously received allogeneic stem cell transplant at any time or received autologous stem cell transplant within 12 weeks of initiating study treatment\n- Participant has plasma cell leukemia, Waldenstrom macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant light-chain amyloidosis\n- \tParticipant is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, active hepatitis A, or active hepatitis C: •\tKnown positive HIV status. •\tSeropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (ie, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR. •\tKnown to be seropositive for hepatitis C virus (HCV); anti-HCV antibody positive or HCV- ribonucleic acid (RNA) quantitation positive, except in the setting of a sustained virologic response (SVR), defined as viremia at least 12 weeks after completion of antiviral therapy\n- Participant is a female who is pregnant or breastfeeding, or who intends to become pregnant during participation in the study.\n- Contraindication to investigational medicinal products (mezigdomide, carfilzomib and dexamethasone)\n- Participation in another interventional study or being in the exclusion period at the end of a previous study\n- Administration of strong CYP3A modulators; administration of proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) within 2 weeks of starting study intervention\n- Participant has any significant medical condition, including active or uncontrolled infection, presence of laboratory abnormality, or psychiatric illness that places the participant at an unacceptable risk for treatment-related complications, if he/she were to participate in the study\n- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days for mild or asymptomatic infections or 28 days for severe/critical illness prior to initiating study intervention (Acute symptoms must have resolved and there are no sequelae that would place the participant at a higher risk of receiving study intervention, based on Investigator assessment in consultation with the Sponsor Medical Monitor)\n- Participant has any condition that confounds the ability to interpret data from the study\n- Participant has any of the following laboratory abnormalities: •\tAbsolute neutrophil count (ANC) < 1,000/¬µL. It is not permissible to administer GCSF to achieve minimum ANC levels within 7 days prior to screening complete blood count (CBC) (or within 14 days prior for pegfilgrastim). •\tPlatelet count: < 75,000/¬µL for participants in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 50,000/¬µL for participants in whom ‚â• 50% of bone marrow nucleated cells are plasma cells. Platelet transfusions are not permitted within 7 days prior to screening complete blood count (CBC). •\tHemoglobin < 8 g/dL (< 4.9 mmol/L). •\tEstimated glomerular filtration rate (eGFR) < 30 mL/min or requiring dialysis. eGFR will be calculated using the Modification of Diet in Renal Disease (MDRD) formula (see http://mdrd.com). •\tCorrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L) •\tSerum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5xx upper limit of normal (ULN) •\tSerum total bilirubin > 1.5 x ULN; > 3.0 mg/dL is allowed for participants with documented Gilbert's syndrome.\n- Participant with gastrointestinal disease or surgery (eg, gastric bypass surgery) that may significantly alter the absorption of CC-92480 and/or other oral study intervention.\n- Participant has prior history of malignancies, other than MM, unless the participant has been free of the disease for 5 years with the exception of the following noninvasive malignancies: •\tBasal cell carcinoma of the skin •\tSquamous cell carcinoma of the skin in situ (Stage 0) •\tCarcinoma in situ of the cervix •\tCarcinoma in situ of the breast •\tIncidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative\n- Participant has received immunosuppressive medication within the last 14 days of initiating study intervention. The following are exceptions to this criterion: •\tIntranasal, inhaled, or topical corticosteroids or local corticosteroid injections (eg, intra-articular injection). •\tSystemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or the equivalent (see Table 7.7.2-1). •\tSteroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication).\n- Inability to comply with restrictions and prohibited treatments as listed in Section 7.7: Concomitant Therapy\n- Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population\n- Participant has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide (including ‚â• Grade 3 rash during prior thalidomide or lenalidomide therapy), carfilzomib or dexamethasone or the excipients contained in the formulations, or participant has any contraindications per local prescribing information\n- Participant has impaired cardiac function or clinically significant cardiac disease, including any of the following: •\tMyocardial infarction within 1 year before inclusion, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure New York Heart Association Class III-IV) or pericardial disease. •\tUncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities, including prolongation of QT interval on Screening ECG as defined by a QTc interval > 470 msec using Fridericia's QT correction formula •\tLeft ventricular ejection fraction < 40% as assessed by transthoracic echocardiogram (TTE) or multigated acquisition scan (MUGA)\n- Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific circumstances and only in countries where local regulations permit, a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply, and BMS approval is required)\n- Participants must agree to refrain from donating blood while on study intervention, during dose interruptions, and for at least 28 days following the last dose of study intervention\n- Eligibility criteria for this study have been carefully considered to ensure the safety of the study participants and that the results of the study can be used. It is imperative that participants fully meet all eligibility criteria\n- Participant who has had prior treatment with mezigdomide or carfilzomib\n- Participant has uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment\n- Participant who has had a live vaccine within 3 months of start of study therapy\n- Participant is unable or unwilling to undergo protocol required thromboembolism or antiviral prophylaxis\n- Participant who has had any investigational agents within 28 days or 5 half-lives (whichever is shorter) of initiating study intervention (Participation in another interventional clinical trial concurrent with this study is not permitted, except for those who have completed treatment with the prior investigational agent(s) and are currently in long-term follow-up.)\n- Participant has received Plasmapheresis within the last 28 days of initiating study intervention"}

Primary endpoints

• {"endpoint_text":"- The progression-free survival defined as the time from inclusion to first documentation of progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma or death due to any cause, whichever occurs first","definition_or_measurement_approach":"Defined as the time from inclusion to first documentation of progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma or death due to any cause, whichever occurs first"}

Secondary endpoints

• {"endpoint_text":"- Overall Survival (OS) defined as the time from inclusion to time of death due to any cause","definition_or_measurement_approach":"Defined as the time from inclusion to time of death due to any cause"}
• {"endpoint_text":"- Overall Response Rate (ORR) defined as the percentage of participants who achieve best response of partial response (PR) or better according to the IMWG Uniform Response Criteria for Multiple Myeloma","definition_or_measurement_approach":"Defined as the percentage of participants who achieve best response of partial response (PR) or better according to the IMWG Uniform Response Criteria for Multiple Myeloma"}
• {"endpoint_text":"- Rate of very good partial response (VGPR) or better (VGPRR) defined as the percentage of participants who achieve best response of VGPR or better according to the IMWG Uniform Response Criteria for Multiple Myeloma","definition_or_measurement_approach":"Defined as the percentage of participants who achieve best response of VGPR or better according to the IMWG Uniform Response Criteria for Multiple Myeloma"}
• {"endpoint_text":"- Rate of complete response (CR) or better (CRR) defined as the percentage of participants who achieve best response of CR or better according to the IMWG Uniform Response Criteria for Multiple Myeloma","definition_or_measurement_approach":"Defined as the percentage of participants who achieve best response of CR or better according to the IMWG Uniform Response Criteria for Multiple Myeloma"}
• {"endpoint_text":"- Time to Response (TTR) defined as the time from inclusion on to the first documentation of response (PR or better)","definition_or_measurement_approach":"Defined as the time from inclusion to the first documentation of response (PR or better)"}
• {"endpoint_text":"- Duration of Response (DOR) defined as the time from the first documentation of response (PR or better) to the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first","definition_or_measurement_approach":"Defined as the time from the first documentation of response (PR or better) to the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first"}
• {"endpoint_text":"- Time to Progression (TTP) defined as the time from inclusion to the first documentation of PD","definition_or_measurement_approach":"Defined as the time from inclusion to the first documentation of progressive disease (PD)"}
• {"endpoint_text":"- Time to Next Treatment (TTNT) defined as the time from inclusion to the start of the next anti-myeloma treatment","definition_or_measurement_approach":"Defined as the time from inclusion to the start of the next anti-myeloma treatment"}
• {"endpoint_text":"- To evaluate minimal residual disease (MRD) negativity rate in participants treated with 480Kd defined as the proportion of participants who achieve CR or better and are MRD negative (defined at a sensitivity of a minimum of 1 in 105 nucleated cells)","definition_or_measurement_approach":"Defined as the proportion of participants who achieve CR or better and are MRD negative (defined at a sensitivity of a minimum of 1 in 10^5 nucleated cells)"}
• {"endpoint_text":"- To evaluate safety of 480Kd in participants with RRMM, defined as the type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment","definition_or_measurement_approach":"Safety assessed by type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment"}
• {"endpoint_text":"- To evaluate cancer and multiple myeloma-related symptoms and health-related quality of life (HRQoL) using the European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30) and the European Quality of Life Multiple Myeloma module (EORTC QLQ-MY20) in participants treated with 480Kd","definition_or_measurement_approach":"Patient-reported HRQoL measured using EORTC QLQ-C30 and EORTC QLQ-MY20 instruments"}

France

Earliest CTIS Part Ii Submission Date

16-02-2026

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

63

Number Of Sites

15

Number Of Participants

70

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France