A multicenter phase 2 study of Belantamab mafodotin and Mezigdomide in combination with a phase Ib Safety run in patients with relapsed multiple myeloma following BCMA-targeting CAR-T cells or bispecific antibodies - The IFM 2024-01 clinical trial (BELAMI)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Saint Etienne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2026-04-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GSK · BMS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To determine the median progression-free survival (PFS) of treatment with belamaf and mezigdomide in combination with dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) following previous treatment with BCMA-targeting CAR-T cells and/or bispecific antibodies.

Secondary objectives 12

1. The overall response rate (ORR)
2. The percentage of patients achieving very good partial response (VGPR) or better response, complete response (CR), and partial response (PR)
3. The time to response (TTR)
4. The duration of response (DOR)
5. The Overall survival (OS)
6. The Time to progression (TTP)
7. The Time to next treatment (TNT)
8. The Time-to-treatment failure (TTF)
9. Rate of therapy-related adverse events, particularly ocular events, to understand corneal safety and tolerability
10. Changes in the Ocular Surface Disease Index (OSDI)
11. Management of ocular adverse events (AEs)
12. Investigating objectives related to the biobank, to enhance the understanding of the biological underpinnings of treatment response and resistance.

Conditions and MedDRA coding

Relapsed/refractory multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Participant must be 18 years of age inclusive at the time of signing the Informed Consent Form (ICF)
2. Participant has a histologically or cytologically confirmed diagnosis of MM as defined by IMWG criteria (Rajkumar 2016)
3. Participant has Eastern Cooperative Oncology Group (ECOG) performance status of score of 0, 1, or 2
4. 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
5. Participant has measurable disease with at least one of the following criteria: • Serum M protein >0.5 g/dL (>5 g/L), or • Urine M protein >200 mg/24h, or • Serum 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)
6. 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
7. Documented presence of BCMA
8. No active bacterial, viral, or fungal infection(s).
9. 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
10. Participant must have adequate organ function at minimum, defined in Table 2 “adequate organ function”. More restrictive parameters are also acceptable if needed
11. Life expectancy of at least 6 months, in the opinion of the investigator
12. Sex and Contraceptive/Barrier Requirements
13. Participants must adhere to contraceptive guidelines on contraception methods in clinical studies to minimize the risk of pregnancy
14. Signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
15. Participant affiliated to or a beneficiary of a social security category
16. 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: - Is not a woman of childbearing potential (WOCBP) as defined in Appendix 7, or - Is 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. - A 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). - The 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.
17. 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: - Refrain from donating sperm - PLUS either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR - Must agree to use contraception/barrier as detailed below: - Agree 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).

Exclusion criteria 26

1. 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
2. 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
3. Evidence of active mucosal or internal bleeding
4. 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
5. Evidence of cardiovascular risk including any of the following: • Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities such as second degree (Mobitz Type II) or third degree atrioventricular (AV) block. • History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of screening. • Class III or IV heart failure as defined by the New York Heart Association functional classification system (see Appendix 8). • Uncontrolled hypertension.
6. 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
7. 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
8. Active infection requiring antibiotic, antiviral, or antifungal therapy
9. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening
10. Current corneal epithelial disease except mild punctuate keratopathy
11. 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
12. 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
13. Patients have to use strong CYP3A4/5 modulators
14. Participant is a pregnant or lactating female
15. Participants with known HIV infection are excluded, unless the following criteria are met: • Established antiretroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL • CD4+ T-cell (CD4+) counts ≥350 cells/µL • No history of AIDS-defining opportunistic infections within the last 12 months
16. 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: • Also note that the presence of hepatitis B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant. • Patients with hepatitis B virus (HBV) will be excluded unless the following criteria (Table 3) can be met:
17. 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: • Participants 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. • 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 unless the participant can meet the following criteria : • RNA test negative • Successful antiviral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks
18. Prior treatment with an antibody-drug conjugate
19. Prior treatment with mezigdomide
20. Prior allogenic stem cell transplant
21. Any major surgery within 4 weeks before the first dose of study drug (or 2 weeks if clinically stable)
22. Has received a live or attenuated vaccine within 30 days before the first dose of study treatment
23. Participant has received plasmapheresis ≤7 days before the first dose of study treatment
24. Presence of active renal condition (infection, requirement for dialysis, or any other condition that could affect participant’s safety).
25. Patient under guardianship or conservatorship
26. Patients with insufficient proficiency in French to understand the study information

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 12

1. ORR, defined as CR or VGPR or PR, according to the IMWG criteria at the time of data cutoff
2. % VGPR or better, CR, VGPR, PR, PD defined according to the IMWG criteria at the time of data cutoff
3. Time to response measured from the start date of treatment to the date of first response according to the IMWG criteria
4. Response duration measured from the start date of treatment to the date of first progression according to the IMWG criteria
5. 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
6. TTP defined as time from the start date of treatment until objective tumor progression date
7. TNT defined as the time from the start date of treatement to the start of the next-line treatment
8. TTF, defined as time from the start date of treatement to discontinuation of therapy for any reason including death, progression, toxicity
9. 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
10. Simplified OSDI (Ocular Surface Disease Index)
11. Ocular AE management (treatment: belamaf dose and schedule modification)
12. Investigating exploratory endpoints related to the biobank

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Saint Etienne

Sponsor organisation

Centre Hospitalier Universitaire De Saint Etienne

Address

St Priest En Jarez, 25 Boulevard Pasteur 25 Boulevard Pasteur

City

St Etienne Cedex 2

Postcode

42055

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

Project Manager

Public contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

Project Manager

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Results and documents

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

Documents 10 files

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

Application history

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