BELANTAMAB MAFODOTIN for Relapsed/refractory multiple myeloma

Inclusion criteria

• {"criterion_text":"- Participant must be 18 years of age inclusive at the time of signing the Informed Consent Form (ICF)\n- Participant must have adequate organ function at minimum, defined in Table 2 “adequate organ function”. More restrictive parameters are also acceptable if needed\n- Life expectancy of at least 6 months, in the opinion of the investigator\n- Sex and Contraceptive/Barrier Requirements\n- Participants must adhere to contraceptive guidelines on contraception methods in clinical studies to minimize the risk of pregnancy\n- Signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol\n- Participant affiliated to or a beneficiary of a social security category\n- Female Participants : A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies: -\tIs not a woman of childbearing potential (WOCBP) as defined in Appendix 7, or -\tIs a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency (as described in Appendix 7 Contraception Guidance) during the intervention period and for at least 4 months after the last dose of study intervention, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. -\tA WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours before the first dose (Cycle 1 Day 1) of study treatment and agree to use a highly effective method of contraception during the study and for 4 months after the last dose of belamaf and for 3 months after mezigdomide. Additional requirements for pregnancy testing during and after study treatment are provided in the Schedule of Activities (SoA) (Appendix 1). -\tThe investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.\n- Male Participants Male participants are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of any altered sperm: -\tRefrain from donating sperm -\tPLUS either: -\tBe abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR -\tMust agree to use contraception/barrier as detailed below: -\tAgree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year, as when having sexual intercourse with a WOCBP (including pregnant females).\n- Participant has a histologically or cytologically confirmed diagnosis of MM as defined by IMWG criteria (Rajkumar 2016)\n- Participant has Eastern Cooperative Oncology Group (ECOG) performance status of score of 0, 1, or 2\n- Participant is considered transplant ineligible or for participants with a history of autologous stem cell transplant (ASCT), ASCT was >100 days before initiating study treatment\n- Participant has measurable disease with at least one of the following criteria: •\tSerum M protein >0.5 g/dL (>5 g/L), or •\tUrine M protein >200 mg/24h, or •\tSerum free light chain (FLC) assay: Involved FLC level >5 mg/dL (>50 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)\n- Participant is quadruple-class exposed or refractory (anti-CD38 antibody (e.g., daratumumab, isatuximab) alone or in combination, immunomodulatory agent (e.g., lenalidomide, pomalidomide), a proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib) and BCMA-directed CAR-T cells and/or anti-BCMA bispecific antibodies) and has failed at least 3 prior lines of anti-myeloma therapies\n- Documented presence of BCMA\n- No active bacterial, viral, or fungal infection(s).\n- All prior treatment related toxicities (defined by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] Version 5.0) must be Grade ≤1 at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy"}

Exclusion criteria

• {"criterion_text":"- Prior treatment with an anti BCMA targeted therapy within 90 days of receiving the first dose of study drugs, or treatment with an investigational agent or approved systemic anti-myeloma thrapy (including systemic steroids) within 14 days or 5 half-lives of receiving the first dose of study drugs\n- Current corneal epithelial disease except mild punctuate keratopathy\n- Contact lenses are not allowed for participants while they are receiving belamaf treatment. Contact lens use may be restarted after discontinuation of belamaf treatment, provided the eye-care specialist confirms there are no other contraindications\n- A known immediate or delayed hypersensitivity or idiosyncratic reaction to drugs chemically related to belamaf, or mezigdomide or any of the components of the study treatment\n- Patients have to use strong CYP3A4/5 modulators\n- Participant is a pregnant or lactating female\n- Participants with known HIV infection are excluded, unless the following criteria are met: •\tEstablished antiretroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL •\tCD4+ T-cell (CD4+) counts ≥350 cells/µL •\tNo history of AIDS-defining opportunistic infections within the last 12 months\n- Patients with a presence of hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) at screening or within 3 months before first dose of study treatment should be excluded unless the following criteria described below are met: •\tAlso note that the presence of hepatitis B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant. •\tPatients with hepatitis B virus (HBV) will be excluded unless the following criteria (Table 3) can be met:\n- Participants with a positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before first dose of study treatment are excluded unless the following conditions are met: •\tParticipants with a positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C RNA test is obtained. •\tPositive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before first dose of study treatment unless the participant can meet the following criteria : •\tRNA test negative •\tSuccessful antiviral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks\n- Prior treatment with an antibody-drug conjugate\n- Prior treatment with mezigdomide\n- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with participant’s safety, obtaining informed consent, or compliance with the study procedures\n- Prior allogenic stem cell transplant\n- Any major surgery within 4 weeks before the first dose of study drug (or 2 weeks if clinically stable)\n- Has received a live or attenuated vaccine within 30 days before the first dose of study treatment\n- Participant has received plasmapheresis ≤7 days before the first dose of study treatment\n- Presence of active renal condition (infection, requirement for dialysis, or any other condition that could affect participant’s safety).\n- Patient under guardianship or conservatorship\n- Patients with insufficient proficiency in French to understand the study information\n- Evidence of active mucosal or internal bleeding\n- Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice\n- Evidence of cardiovascular risk including any of the following: •\tEvidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities such as second degree (Mobitz Type II) or third degree atrioventricular (AV) block. •\tHistory of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of screening. •\tClass III or IV heart failure as defined by the New York Heart Association functional classification system (see Appendix 8). •\tUncontrolled hypertension.\n- Participant has malignancies other than the disease under study are excluded, except for any other malignancy from which the participant has been disease free for >5 years with the exception of the following noninvasive malignancies: basal or squamous cell skin carcinoma, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological findings of prostate cancer (T1a or T1b using the tumor, nodes, and metastases clinical staging system), or prostate cancer that is curative\n- Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belamaf or mezigdomide or any other components of the study treatment\n- Active infection requiring antibiotic, antiviral, or antifungal therapy\n- Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening"}

Primary endpoints

• {"endpoint_text":"- Defined as the duration from the start date of treatement to the date of either progressive disease, or death, whichever occurs first. Progressive disease will be evaluated as defined by 2016 IMWG response criteria (Kumar et al. 2016), as data permits, and assessed by the investigator. If the subject is responder or the status is unknown at last contact, then the subject’s data will be censored at the date the subject was last known to be non-progressive","definition_or_measurement_approach":"Duration from start date of treatment to date of progressive disease or death, whichever occurs first; progressive disease evaluated per 2016 IMWG response criteria and assessed by investigator; responders or unknown status at last contact are censored at last known non-progressive date."}

Secondary endpoints

• {"endpoint_text":"- ORR, defined as CR or VGPR or PR, according to the IMWG criteria at the time of data cutoff","definition_or_measurement_approach":"Overall response rate (ORR) defined as complete response (CR) or very good partial response (VGPR) or partial response (PR) per IMWG criteria at data cutoff."}
• {"endpoint_text":"- % VGPR or better, CR, VGPR, PR, PD defined according to the IMWG criteria at the time of data cutoff","definition_or_measurement_approach":"Proportions of patients achieving VGPR or better, CR, VGPR, PR, progressive disease (PD) per IMWG criteria at data cutoff."}
• {"endpoint_text":"- Time to response measured from the start date of treatment to the date of first response according to the IMWG criteria","definition_or_measurement_approach":"Time from treatment start to first documented response as per IMWG criteria."}
• {"endpoint_text":"- Response duration measured from the start date of treatment to the date of first progression according to the IMWG criteria","definition_or_measurement_approach":"Duration from treatment start to first progression per IMWG criteria."}
• {"endpoint_text":"- OS measured from the start date of treatment to the date of the subject’s death. If the subject is alive or the vital status is unknown at last contact, then the subject’s data will be censored at the date the subject was last known to be alive","definition_or_measurement_approach":"Overall survival measured from treatment start to death; alive/unknown censored at last known alive date."}
• {"endpoint_text":"- TTP defined as time from the start date of treatment until objective tumor progression date","definition_or_measurement_approach":"Time from treatment start to objective tumor progression date."}
• {"endpoint_text":"- TNT defined as the time from the start date of treatement to the start of the next-line treatment","definition_or_measurement_approach":"Time from treatment start to initiation of next-line therapy."}
• {"endpoint_text":"- TTF, defined as time from the start date of treatement to discontinuation of therapy for any reason including death, progression, toxicity","definition_or_measurement_approach":"Time from treatment start to discontinuation of therapy for any reason (death, progression, toxicity, etc.)."}
• {"endpoint_text":"- Assessing therapy-related adverse events according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0), particularly ocular events, to understand corneal safety and tolerability","definition_or_measurement_approach":"Adverse events assessed and graded per NCI CTCAE v5.0, with focus on ocular events and corneal safety/tolerability."}
• {"endpoint_text":"- Simplified OSDI (Ocular Surface Disease Index)","definition_or_measurement_approach":"Assessment using the simplified OSDI instrument to measure ocular surface disease symptoms."}
• {"endpoint_text":"- Ocular AE management (treatment: belamaf dose and schedule modification)","definition_or_measurement_approach":"Assessment of ocular adverse event management including belamaf dose/schedule modifications."}
• {"endpoint_text":"- Investigating exploratory endpoints related to the biobank","definition_or_measurement_approach":"Exploratory analyses related to biobank specimens to investigate biological underpinnings of response and resistance."}

Other endpoints

• {"endpoint_text":"- Investigating exploratory endpoints related to the biobank","definition_or_measurement_approach":"Exploratory biobank-related objectives to enhance understanding of biological underpinnings of treatment response and resistance."}

France

Earliest CTIS Part Ii Submission Date

30-01-2026

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

69

Number Of Sites

30

Number Of Participants

44

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Saint Etienne

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"GSK","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"BMS","duties_or_roles":"Source of monetary support","organisation_type":""}