Newly diagnosed patients with multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Blenrep
Product Name: Belantamab Mafodotin
Product Code: GSK2857916
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Belantamab mafodotin
CAS Numb
Sponsors
Hellenic Society of Hematology (EAE)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants >18 of age. 2. Monoclonal plasma cells in BM =10% or presence of biopsy proven plasmacytoma and documented MM satisfying =1 of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria: CRAB criteria: i. Hypercalcemia: serum calcium >0.25 mmol/L higher than ULN or >2.75 mmol/L. ii. Renal insufficiency: CrCl 177 µmol/L. iii. Anemia: hemoglobin >2 g/dL below the LLN or hemoglobin 1 focal lesion on MRI. 3. Must have =1 aspect of measurable disease: o Urine M-protein excretion =200 mg/24 hrs, or o Serum M-protein concentration =0.5 g/dL, or o sFLC assay: involved FLC level =10 mg/dL and abnormal sFLC ratio (1.65). 4. Not a candidate for high-dose chemotherapy with ASCT due to presence of significant comorbid condition(s). The patients will be assessed by the IMWG frailty index, ESMO guidelines. Patients with IMWG frailty index score 1/2 will be considered transplant ineligible. 5. ECOG PS of 0-2. 6. Adequate organ system function as defined by the below: Hematologic o ANC =1.25X109/L; G-CSF use for the past 14 days is NOT allowed. o Hemoglobin =8.0 g/dL; transfusions are not permitted in the past 14 days prior to the assessment. Erythropoietin use is allowed. o Platelet count =50x109/L if the BM is >50%. Otherwise, =75x109/L; transfusions or platelet stimulating agents are NOT allowed in the past 14 days prior to the assessment. Hepatic o Total bilirubin =1.5xULN (isolated bilirubin =1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 1 year. b. Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation. c. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of actual procedure or confirmed by ultrasound. Tubal ligation must be confirmed with medical records. OR • WOCBP and using two methods of reliable birth control, beginning 4 weeks before initiating lenalidomide, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of lenalidomide. WOCBP participants must use one method of reliable birth control that is highly effective for 4 months following discontinuation of belantamab mafodotin. WOCBP must also agree not to donate eggs, during dose interruptions and for 28-days following last dose of lenalidomide or 4 months following discontinuation of belantamab mafodotin whichever is longer. WOCBP must have two negative pregnancy tests before therapy. The first test should be performed <10-1
Exclusion criteria
Exclusion criteria: 1. Prior systemic therapy for MM/SMM. o NOTE 1: An emergency course of steroids permitted. o NOTE 2: Focal palliative radiation permitted prior to enrollment, provided occurred =2 weeks before first drug, participant has recovered from radiation-related toxicities, and participant did not require corticosteroid administration for radiation-induced AEs. 2. Peripheral neuropathy or neuropathic pain =Grade 2, as defined by NCI-CTCAE V.5. 3. Major surgery within 4 weeks before first dose. o NOTE 1: Patients who underwent major surgery must be clinically stable to be enrolled. o NOTE 2: Major surgery shall be defined based on Investigator’s judgment. 4. Presence of active renal condition. Participants with isolated proteinuria resulting from MM are eligible, provided they meet other inclusion criteria. 5. Any serious and/or unstable pre-existing medical or psychiatric disorder, or other conditions that could interfere with participant’s safety, obtaining informed consent, or compliance to procedures. 6. Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy. 7. Current active liver or biliary disease (except Gilbert’s syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per Investigator’s assessment). 8. Participants with previous or concurrent malignancies other than MM. Exceptions are surgically treated cervical carcinoma in situ, or other malignancy that's been considered medically stable for =2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. o NOTE: Participants with cured non-melanoma skin cancer are allowed without 2-year restriction. 9. Evidence of cardiovascular risk including any of: • Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities, second degree, or third degree atrioventricular block. • History of myocardial infarction, acute coronary syndromes, coronary angioplasty, or stenting or bypass grafting =3 months of Screening. 10. Class III/IV heart failure as defined by NYHA. 11. Uncontrolled hypertension. 12. Active infection requiring treatment. 13. Known HIV infection, unless the participant can meet all of following: • Established ART for =4 weeks and HIV viral load <400 copies/mL. • CD4+ T-cell (CD4+) count =350 cells/uL. • No history of AIDS-defining opportunistic infections =12 months. o NOTE: consideration must be given to ART and prophylactic antimicrobials that may have a drug:drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products. 14. Seropositivity for hepatitis B. o NOTE 1: Participants with resolved infection. PCR positive excluded. o NOTE 2: Presence of antiHBs indicating previous vaccination will not be excluded. 15. Positive HCV antibody test result or positive HCV RNA test result at screening or =3 months before first dose of treatment unless participant meets the following: • RNA test negative • Successful anti-viral treatment required, followed negative HCV RNA test after washout period =4 weeks. 16. Current corneal epithelial disease except for mild punctate keratopathy. o NOTE: Participants with mild punctate keratopathy allowed. 17. Intolerance or contraindications to anti-viral prophylaxis. 18. Unable to tolerate antithrombotic prophylaxis. 19. AL amyloidosis, active POEMS syndrome or active plasma cell leukemia at screening. 20. Exhib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Part 1 • Number of participants with dose-limiting toxicities (DLTs). • Number of participants with AEs and serious adverse events (SAEs). • Number of participants with Grade 2 or above Keratopathy Visual Acuity (KVA) scale events Part 2 • Overall Response Rate as per IMWG by Investigator Assessment. • Number of participants with AEs and SAEs. ;Main Objective: Part 1 – Dose finding: To determine the safety and tolerability of belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat and to establish a recommended phase 2 dose for participants with transplant ineligible (TI) NDMM. Part 2 – Dose expansion: To further evaluate the safety and determine the preliminary clinical activity of the belantamab mafodotin RP2D in combination with lenalidomide, dexamethasone and nirogacestat.;Secondary Objective: To evaluate the effect of combining belantamab mafodotin with lenalidomide, dexamethasone and nirogacestat: • To assess the efficacy of belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat in patients with transplant ineligible newly diagnosed multiple myeloma. • To evaluate alternate corneal AE management approach using the Alternate Dose Modification Guidelines for belantamab mafodotinrelated ocular adverse events • To further characterize the pharmacokinetic (PK) profile of belantamab mafodotin when administered in combination with lenalidomide, dexamethasone and nirogacestat. • To characterize the PK profile of nirogacestat when administered in combination with belantamab mafodotin, lenalidomide and dexamethasone. • To evaluate symptomatic corneal AEs measured by the OSDI questionnaire as documented by the investigator. • To evaluate Vision-related functioning measured by the Vision Related Anamnestic Tool as documented by the investigator ;Timepoint(s) of evaluation of this end point: During the whole study duration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 & 2 • Lenalidomide Relative Dose Intensity (RDI). • Nirogacestat RDI. • Cumulative administered dose of belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat. • Overall Response Rate as per IMWG by Investigator Assessment (secondary endpoint for Part 1). • Time to Response (TTR) as per IMWG by Investigator Assessment. • Duration of Response (DoR) as per IMWG by Investigator Assessment. • Complete Response Rate (CRR) as per IMWG by Investigator Assessment. • Number of participants that achieved at least VGPR. • Minimal residual disease (MRD) negativity rate in the BM, Negative MRD is defined as the absence of tumor plasma cells within 100,000 (Sensitivity 10-5) BM cells. MRD will be assessed via next-generation flow (NGF) cytometry in participants with VGPR or better response. • Progression-free Survival (PFS) as per IMWG by Investigator Assessment. • Overall Survival (OS). • Number of participants with abnormal ocular findings (on ophthalmic exam). • Belantamab mafodotin dose holds. • Number of participants with changes from baseline and proportion of participants with within-participant meaningful change in ocular self-reported symptoms and related impacts as measured by the OSDI questionnaire (Part 1 only; DLT evaluable population). • Number and proportion of participants with changes from baseline in ocular symptoms and related impacts as measured by the Vision Related Anamnestic Tool (Part 2 only; Safety population). • Observed PK concentrations for belantamab mafodotin. • Observed PK concentrations for nirogacestat.;Timepoint(s) of evaluation of this end point: During the whole study duration. | — |
Countries
Greece
Contacts
Public ContactProf. Evangelos Terpos
Hellenic Society of Hematology (EAE)
Outcome results
None listed