Relapsed/refractory multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Belantamab Mafodotin
Product Code: GSK2857916
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Belantamab mafodotin
CAS Number: 2050232-20-5
Oth
Sponsors
Hellenic Society of Hematology (EAE)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be =18 years. 2. Documented diagnosis of MM as per IMWG criteria. 3. Must have at least ONE aspect of measurable disease, 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 (1.65). 4. ECOG performance status of 0–2. 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 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-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. In
Exclusion criteria
Exclusion criteria: 1. Peripheral neuropathy or neuropathic pain =Grade 2, per NCI CTCAEs V5. 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. 3. Presence of active renal condition. Participants with isolated proteinuria resulting from MM are eligible if they fulfil other inclusion criteria. 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. 5. Active mucosal or internal bleeding uncontrolled by local therapy and unexplained by reversible coagulopathy. 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). 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. 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. 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. 10. Active infection requiring therapy. 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. 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 real-time polymerase chain reaction (PCR), except PCR positive. NOTE: Presence of antiHBs indicating previous vaccination will not constitute an exclusion criterion. 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. 14. Current corneal epithelial disease except for mild punctate keratopathy. NOTE: Mild punctate keratopathy allowed. 15. Intolerance or contraindications to anti-viral prophylaxis. 16. Intolerant to antithrombotic prophylaxis. 17. Active or history of venous thromboembolism within =3 months. 18. AL amyloidosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 To determine the safety and tolerability of belantamab mafodotin in combination with DPd and Pd and to establish theRP2R for patients with RRMM and one to three prior lines of treatment who are lenalidomide refractory. Part 2 To further evaluate the safety and determine the clinical activity of the RP2R in patients with RRMM and one to three prior lines of treatment who are lenalidomide refractory. ;Secondary Objective: To evaluate the effect of combining belantamab mafodotin with DPd and Pd: • Assess the efficacy of belantamab mafodotin in combination with DPd and Pd in patients with RRMM and one to three prior lines of treatment who are lenalidomide refractory. • Evaluate alternate corneal adverse event (AE) management approach using Alternate Dose Modification Guidelines for belantamab mafodotin-related ocular adverse events. • To evaluate the pharmacokinetic (PK) profile of belantamab mafodotin when administered in combination with DPd and Pd. • To evaluate vision-related functioning measured by the Vision Related Anamnestic Tool as documented by the investigator. ;Primary end point(s): Primary Endpoints Part 1 • Number of participants with dose-limiting toxicities (DLTs). • Number of participants with AEs and serious adverse events (SAEs). • Number of participants with ocular toxicity of Grade =2 (per KVA scale). Part 2 • Overall Response Rate (ORR) as per IMWG by Investigator Assessment. • Number of participants with AEs and SAEs. • Number of participants with ocular toxicity of Grade =2 (per KVA scale). ;Timepoint(s) of evaluation of this end point: During the whole study duration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 & 2 • Cumulative administered dose of belantamab mafodotin in combination with daratumumab, pomalidomide, and dexamethasone or in combination with pomalidomide and dexamethasone. • ORR as per IMWG (secondary endpoint for Part 1) • Very Good Partial Response (VGPR) or better (VGPR+) rate. • 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. • 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. • 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. • Belantamab mafodotin observed plasma concentrations. • Number and proportion of participants with changes from baseline in ocular symptoms and related impacts as measured by the Vision Related Anamnestic Tool (only for Part 2). Exploratory Endpoints • Relation between baseline bone marrow B-Cell Maturation Antigen (BCMA) expression levels/soluble BCMA (sBCMA) levels AND clinical response. • Change from baseline of sBCMA levels. • Derived PK parameter values for belantamab mafodotin. • Belantamab mafodotin exposure (e.g., concentration, Cmax, or AUC) vs. efficacy and/or safety endpoints (e.g., ORR, CRR, ocular events), as data permit. • Concordance between the visual acuity score produced by the Peak Acuity app and the best corrected visual acuity score of the ophthalmic exam ;Timepoint(s) of evaluation of this end point: During the whole study duration. | — |
Countries
Greece
Contacts
Public ContactProf. Terpos
Hellenic Society of Hematology (EAE)
Outcome results
None listed