BELANTAMAB MAFODOTIN for Relapsed/refractory multiple myeloma

Inclusion criteria

• {"criterion_text":"- 1. Participant must be ≥18 years.\n- 2. Documented diagnosis of MM as per IMWG 2016 criteria.\n- 3. Must have measurable disease at the time of diagnosis, defined as 1 of following: a. Urine M-protein excretion ≥200 mg/24 hrs (≥0.2 g/24 hrs), or b. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or c. Serum FLC assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).\n- 4. ECOG performance status of 0–2.\n- 5. Adequate organ system function defined by following assessments. Hematologic a. Absolute neutrophil count ≥1.5 X 10^9/L; granulocyte colony stimulating factor use within the past 14 days is NOT permitted. b. Hemoglobin ≥8.0 g/dL; transfusions within the past 14 days are NOT permitted. Erythropoietin use is allowed. c. Platelet count ≥50x10^9/L if bone marrow (BM) is >50% involved in myeloma. Otherwise ≥75x10^9/L; transfusions within the past 14 days are NOT allowed to reach this level. Hepatic a. Total bilirubin ≤1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). b. Alanine aminotransferase ≤2.5xULN. Renal a. Estimate glomerular filtration rate ≥30 mL/min/1.73 m2; calculated using the Modified Diet in Renal Disease formula. b. Spot urine (albumin/creatinine ratio) ≤500 mg/g (56 mg/mmol) OR c. Urine Dipstick: Negative trace; if ≥1+ only eligible if confirmed ≤500 mg/g [56 mg/mmol] by albumin/creatinine ratio.\n- 6. Female participants: contraceptive use should comply with local regulations: A female participant is eligible if not pregnant or breastfeeding, and at least 1 of the following conditions applies: • Is not a woman of childbearing potential (WOCBP) defined as follows: a. ≥45 years and has not had menses for >1 year. b. Participants who have been amenorrhoeic for <2 years without history of hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range at screening. c. Post-hysterectomy, post-bilateral oophorectomy, or post-bilateral tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the procedure or confirmed by ultrasound. Tubal ligation must be confirmed with medical records of procedure. OR • WOCBP and using two methods of reliable birth control (1 method that is highly effective and 1 additional effective [barrier] method), beginning 4 weeks before starting treatment with pomalidomide, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of pomalidomide treatment. WOCBP participants must use 1 method of reliable birth control that is highly effective for 4 months following discontinuation of belantamab mafodotin or 3 months following the discontinuation of daratumumab. WOCBP must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during treatment, during dose interruptions and for 28-days following the last dose of pomalidomide or 3 months following discontinuation of daratumumab treatment or 4 months following discontinuation of belantamab mafodotin treatment whichever longer. WOCBP must have two negative pregnancy tests before starting therapy. First test should be performed within 10–14 days and the second test ≤ 24 hours before the start of pomalidomide. Participant should not receive pomalidomide until investigator has verified that results of pregnancy tests are negative. Investigator should evaluate effectiveness of the contraceptive method in relationship to first dose of treatment. Investigator is responsible for a review of medical history, menstrual history, and recent sexual activity to decrease risk for inclusion of woman with a nearly undetected pregnancy.\n- 7. Male participants: contraceptive use should be consistent with local regulations regarding methods of contraception for participants: Male participants are eligible if they agree to the following during the intervention period and until 28 days after the last dose of pomalidomide or 3 months following discontinuation of daratumumab or 6 months after last dose of belantamab mafodotin, whichever is longer, to allow for clearance of any altered sperm. • Refrain from donating sperm + either: • Be abstinent from heterosexual intercourse as preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain, OR • Must agree to contraception as detailed: Agree to a male condom, even if they have undergone successful vasectomy, and female partner to use additional highly effective contraceptive method with failure rate of <1% per year as when having sexual intercourse with WOCBP (including pregnant females).\n- 8. Participants must be able to understand the study procedures and agree to participate in study by providing written informed consent and have received 1 to 3 prior lines of therapy (including lenalidomide) and be lenalidomide refractory at any lenalidomide dose."}

Exclusion criteria

• {"criterion_text":"- 1. Peripheral neuropathy or neuropathic pain ≥Grade 2, per NCI CTCAEs V5.\n- 7. Participants with previous or concurrent malignancies other than MM are excluded, except surgically treated cervical carcinoma in situ, or any other malignancy that has been considered medically stable for ≥2 years. The participant must not receive therapy, other than hormonal. NOTE: Participants with cured non-melanoma skin cancer are allowed without restriction.\n- 8. Evidence of cardiovascular risk including any of the following: • Current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities, second degree or third degree atrioventricular block. • Screening 12-lead ECG showing a baseline QT interval >470msec. • History of myocardial infarction, acute coronary syndromes, coronary angioplasty, or stenting or bypass grafting within 3 months of Screening. • Class III/IV heart failure per NYHA functional classification system. • Uncontrolled hypertension.\n- 9. Participant has known chronic obstructive pulmonary disease (COPD; defined as a forced expiratory volume in 1 second [FEV1] <50% of predicted normal), persistent asthma, or history of asthma within ≤2 years.\n- 13. Positive hepatitis C virus (HCV) antibody test result or HCV RNA test result at screening or ≤3 months before the first dose of study drug unless participant meets the following: • RNA test negative • Successful anti-viral treatment (8 weeks), following negative HCV RNA test after ≥4 weeks.\n- 14. Current corneal epithelial disease except for mild punctate keratopathy. NOTE: Mild punctate keratopathy allowed.\n- 15. Intolerance or contraindications to anti-viral prophylaxis.\n- 16. Intolerant to antithrombotic prophylaxis.\n- 17. Active or history of venous thromboembolism within ≤3 months.\n- 18. AL amyloidosis, active POEMS syndrome or active plasma cell leukemia at screening.\n- 19. Prior allogeneic stem cell transplantation.\n- 10. Active infection requiring therapy.\n- 20. Clinical signs or history of meningeal or central nervous system involvement by MM.\n- 21. Intolerance, immediate or delayed hypersensitivity reaction or idiosyncratic reaction to: drugs chemically related to belantamab mafodotin, or any of the components of the study treatment; daratumumab SC or to any of its excipients; or infused protein products,sucrose, histidine, and polysorbate 80.\n- 22. Investigational drug within 14 days or 5 half-lives (whichever shonrter) preceding first study drug.\n- 23. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drug.\n- 24. Participant who has received prior treatment with pomalidomide, belantamab mafodotin or other BCMA targeted agent areexcluded.\n- 25. Plasmapheresis within 7 days before the first dose of study drug.\n- 26. Participants with uncontrolled skin disease.\n- 27. Participant must not have received a live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.\n- 28. Participant should not use contact lenses while receiving belantamab mafodotin. Because of the embryo-fetal risk of pomalidomide, all participants must adhere to the pomalidomide Pregnancy Prevention Program applied in their region as per label. The Sponsor will review and approve the participant eligibility data submitted by the investigational site before dosing.\n- 11. Known HIV infection, unless participant meets all following: • Established anti-retroviral therapy (ART) for ≥4 weeks and HIV viral load <400 copies/mL. • CD4+ T-cell count ≥350 cells/uL. • No history of acquired immunodeficiency syndrome-defining opportunistic infections within the last year.\n- 12. To be seropositive for hepatitis B at screening or ≤3 months prior to first study drug dose. NOTE: Participants with resolved infection must be screened using realtime polymerase chain reaction (PCR), except PCR positive. NOTE: Presence of antiHBs indicating previous vaccination will not constitute an exclusion criterion.\n- 2. Major surgery within 4 weeks before 1st dose. NOTE: must be clinically stable following major surgery. NOTE: major surgery shall be defined by Investigator.\n- 3. Presence of active renal condition. Participants with isolated proteinuria resulting from MM are eligible if they fulfil other inclusion criteria.\n- 4. Any serious and/or unstable pre-existing medical or psychiatric disorder, or other conditions that may interfere with participant's safety, obtaining informed consent or complying to procedures.\n- 5. Active mucosal or internal bleeding uncontrolled by local therapy and unexplained by reversible coagulopathy.\n- 6. Current active unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis (except for Gilbert's syndrome or asymptomatic gallstones; otherwise, stable non-cirrhotic chronic liver disease; or hepatobiliary involvement of malignancy as per Investigator)."}

Primary endpoints

• {"endpoint_text":"- • Number of participants with dose-limiting toxicities (DLTs).\n- • Number of participants with AEs and serious adverse events (SAEs).\n- • Number of participants with ocular toxicity of Grade ≥2 (per KVA scale).\n- Part 2 • Overall Response Rate (ORR) as per IMWG by Investigator Assessment.\n- • Number of participants with AEs and SAEs.\n- • Number of participants with ocular toxicity of Grade ≥2 (per KVA scale).","definition_or_measurement_approach":"Dose-limiting toxicities (DLTs): reported as number of participants experiencing DLTs. Adverse events (AEs) and serious adverse events (SAEs): counted as number of participants with AEs/SAEs. Ocular toxicity Grade ≥2 assessed per Keratopathy Visual Acuity (KVA) scale. Overall Response Rate (ORR): assessed as per IMWG 2016 by Investigator Assessment."}

Secondary endpoints

• {"endpoint_text":"- • Cumulative administered dose of belantamab mafodotin in combination with daratumumab, pomalidomide, and dexamethasone or in combination with pomalidomide and dexamethasone.","definition_or_measurement_approach":"Cumulative administered dose measured as total amount of belantamab mafodotin administered per participant across treatment."}
• {"endpoint_text":"- • ORR as per IMWG 2016","definition_or_measurement_approach":"Overall Response Rate assessed according to IMWG 2016 criteria."}
• {"endpoint_text":"- • Very Good Partial Response (VGPR) or better (VGPR+) rate.","definition_or_measurement_approach":"VGPR+ rate measured per IMWG response criteria."}
• {"endpoint_text":"- • Time to Response (TTR) as per IMWG 2016 by Investigator assessment.","definition_or_measurement_approach":"Time from first dose to first documented response per IMWG 2016 by investigator assessment."}
• {"endpoint_text":"- • Duration of Response (DoR) as per IMWG 2016 by Investigator assessment.","definition_or_measurement_approach":"Duration from first documented response to progression per IMWG 2016 by investigator assessment."}
• {"endpoint_text":"- • Complete Response Rate (CRR) as per IMWG 2016 by Investigator assessment.","definition_or_measurement_approach":"Complete response rate per IMWG 2016 assessed by investigator."}
• {"endpoint_text":"- • Minimal residual disease (MRD) negativity rate in the BM, Negative MRD is defined as the absence of tumor plasma cells in minimum 100,000 (105) BM cells. MRD will be assessed via next-generation flow (NGF) cytometry in participants with VGPR or better response.","definition_or_measurement_approach":"MRD negativity defined as absence of tumor plasma cells in ≥100,000 bone marrow cells; assessed by NGF cytometry in participants with VGPR or better."}
• {"endpoint_text":"- • Progression-Free Survival (PFS) as per IMWG 2016 by Investigator assessment.","definition_or_measurement_approach":"PFS measured from first dose to documented disease progression or death per IMWG 2016 by investigator assessment."}
• {"endpoint_text":"- • Overall Survival (OS).","definition_or_measurement_approach":"Overall survival measured from first dose to death from any cause."}
• {"endpoint_text":"- • Number of participants with abnormal ocular findings (on ophthalmic exam).","definition_or_measurement_approach":"Count of participants with abnormal findings on ophthalmic examination."}
• {"endpoint_text":"- • Belantamab mafodotin dose holds.","definition_or_measurement_approach":"Number of occurrences and participants with dose holds of belantamab mafodotin."}
• {"endpoint_text":"- • Belantamab mafodotin observed plasma concentrations.","definition_or_measurement_approach":"Plasma concentration measurements of belantamab mafodotin collected per PK schedule."}
• {"endpoint_text":"- • Number and proportion of participants with changes from baseline in ocular symptoms and related impacts as measured by the Vision Related Anamnestic Tool.","definition_or_measurement_approach":"Changes from baseline in ocular symptoms measured using the Vision Related Anamnestic Tool as documented by investigator."}

Greece

Earliest CTIS Part Ii Submission Date

30-09-2024

Latest Decision Or Authorization Date

26-02-2026

Processing Time Days

514

Number Of Sites

3

Number Of Participants

12

Primary sponsor

Full Name

Hellenic Society Of Hematology

Organisation Type

Patient organisation/association

Country Of Registered Address

Greece

Contract research organisations

Name

Syneos Health Inc.

Responsibilities

Primary/surrogate endpoint testing; PK analysis (ADC, total mAb and/or cysmcMMAF) per CTIS sponsorDuties

Name

Almac Clinical Services Limited

Responsibilities

Operational services (code 14) per CTIS sponsorDuties

Name

Health Data Specialists Ireland Limited

Responsibilities

Contracts with sites and vendors; trial operations and data services (codes 1,10,11,12,15,6,7,8 as listed in CTIS sponsorDuties)

Name

Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.

Responsibilities

Operational support activities (codes 1,12,8 listed in CTIS sponsorDuties)

Third parties

• {"country":"Greece","full_name":"Geka Aliki","duties_or_roles":"Ophtalmological Examination (code 15)","organisation_type":"Health care"}
• {"country":"Greece","full_name":"Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.","duties_or_roles":"codes: 1, 12, 8 (no textual duties provided in CTIS entry)","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Istodierevnitiki S.A.","duties_or_roles":"Histopathology (code 15); code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"Chemical chemistry; Clinical microbiology; Serology/ endocrinology; ECG analysis/ review; Medical image analysis/ review - X-ray, MRI, ultrasound, etc.; Primary/ surrogate endpoint test (code 15); code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"Primary/ surrogate endpoint test; PK analysis (ADC, total mAb and/or cysmcMMAF), sBCMA, antibodies produced against belantamab (code 15); code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Genotypos Private Diagnostic Laboratory Of Molecular And Cytogenetic Analysis S.A.","duties_or_roles":"Histopatholog (code 15); code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Almac Clinical Services Limited","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A. (Thessaloniki address)","duties_or_roles":"Clinical chemistry; Clinical microbiology; Serology/ endocrinology; ECG analysis/ review; Medical image analysis/ review; Primary/ surrogate endpoint test - X-ray, MRI, ultrasound, etc. (code 15); code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Greece","full_name":"Panagiotis Desiris","duties_or_roles":"ophthalmological examination (code 15)","organisation_type":"Health care"}
• {"country":"United Kingdom","full_name":"Glaxo Operations UK Limited","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Primary/surrogate endpoint test; PK analysis (ADC, total mAb and/or cysmcMMAF) (code 15); code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Health Data Specialists Ireland Limited","duties_or_roles":"codes: 1, 10, 11, 12, 15 (Contracts with sites and vendors), 6, 7, 8","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"National And Kapodistrian University Of Athens","duties_or_roles":"Primary/ surrogate endpoint test; MRD assessment (code 15); code 4","organisation_type":"Educational Institution"}
• {"country":"Greece","full_name":"Aktina Private Multimedical-Doctors Office I.K.E.","duties_or_roles":"Ophthalmologic (eye) examinations (code 15)","organisation_type":"Hospital/Clinic/Other health care facility"}