Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: belantamab mafodotin
Product Code: GSK2857916
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: belantamab mafodotin
Current Sponsor code: GSK2857916
Concentrat
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1. Participant must be over 18 years of age. Type of Participant and Disease Characteristics 2. Diagnosis of multiple myeloma with a requirement for treatment as documented per International Myeloma Working Group (IMWG) criteria. Must have at least ONE aspect of measurable disease, defined as one of the following: a. Urine M-protein excretion =200 mg/24 hrs (=0.2g/24 hrs), or b. Serum M-protein concentration =0.5 g/dL (=5.0 g/L), or c. Serum free light chain (FLC) assay: involved FLC level =10 mg/dL (=100 mg/L) and an abnormal serum free light chain ratio (1.65). 3. Not a candidate for high-dose chemotherapy with ASCT due to presence of frailty and/or significant comorbid condition(s), such as cardiac, pulmonary or other major organ dysfunction that are likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation, as judged by the investigator. 4. ECOG status of 0-2 5. Adequate organ system functions as defined by the laboratory assessments listed in the protocol. Sex 6. Male and/or female a. Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: - Is not a woman of childbearing potential (WOCBP) OR -WOCBP participants must use a contraceptive method that is highly effective as detailed in the protocol. b. Male Participants: Male participants are eligible to participate if they agree to the following - Refrain from donating sperm PLUS either: - Be abstinent from heterosexual intercourse OR - Must agree to use contraception/barrier as detailed in the protocol. Informed Consent 7. Capable of giving signed informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 79 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 719
Exclusion criteria
Exclusion criteria: Type of Participant and Disease Characteristics 1. Smoldering multiple myeloma (SMM). 2. Prior systemic therapy for multiple myeloma, or SMM. An emergency course of steroids (defined as no greater than 40 mg of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted. 3. Patient is eligible for high dose chemotherapy with ASCT. Medical Conditions 4. Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the NCI-CTCAE Version 5. 5. Major surgery within 4 weeks prior to the first dose of study drug. 6. Presence of active renal condition (infection, requirement for dialysis or any other significant condition that could affect participant’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil criteria given in the protocol. 7. 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 to the study procedures. 8. Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy. 9. Current active liver or biliary disease (except for Gilbert’s syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per the Investigator’s assessment). 10. Participants with previous or concurrent malignancies other than multiple myeloma are excluded. Exceptions are surgically treated cervical carcinoma in situ, or any other malignancy that has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. Note: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction. 11. Evidence of cardiovascular risk 12. Active infection requiring treatment. 13. Known HIV infection. 14. Presence of hepatitis B surface antigen (HbsAg), or hepatitis B core antibody (HbcAb), at Screening or within 3 months prior to first dose of study treatment. 15. Positive hepatitis C antibody test result. Note: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. 16. Current corneal epithelial disease except for mild punctate keratopathy (Appendix 12 of the protocol). Note: Participants with mild punctate keratopathy are allowed. 17. Intolerance or contraindications to anti-viral prophylaxis. 18. Unable to tolerate antithrombotic prophylaxis. 19. AL amyloidosis (light chain amyloidosis), active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening. 20. Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma. Prior/Concomitant Therapy 21. Use of an investigational drug within 14 days or five half-lives (whichever is longer) preceding the first dose of study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 -Determine safety and tolerability of belantamab mafodotin in combination with VRd to establish a recommended dose for participants with transplant ineligible (TI) newly diagnosed multiple myeloma (NDMM) Part 2 -To compare the efficacy of belantamab mafodotin in combination with VRd with that of VRd alone in participants with TI NDMM;Secondary Objective: Part 1 -Effect of combining belantamab mafodotin with VRd in relation to lenalidomide & bortezomib relative dose intensity (RDI) -To evaluate the pharmacokinetics profile of belantamab mafodotin, when administered in combination with VRd -To assess ADAs against belantamab mafodotin Part 2 -To assess the efficacy of belantamab mafodotin in combination with VRd with that of VRd alone in participants with TI NDMM - To evaluate the safety and tolerability of belantamab mafodotin when administered in combination with VRd -To further characterize the exposure to belantamab mafodotin when administered in combination with VRd -To assess ADAs against belantamab mafodotin - To evaluate and compare changes in HRQOL - To evaluate the safety and tolerability of belantamab mafodotin based on self-reported symptomatic adverse effects when administered in combination with VRd - To evaluate self-reported ocular symptomatic adverse effects of belantamab mafodotin in combination with VRd;Primary end point(s): Part 1 - Number (%) of participants with dose limiting toxicities (DLTs) - Number (%) of participants with adverse events (AEs) Part 2 - Minimal Residual Disease (MRD) negativity rate, defined as the percentage of participants who are MRD negative by next-generation sequencing (NGS) with sensitivity of 10-5 - PFS, defined as the time from the date of randomization until the earliest date of documented disease progression or death due to any cause ;Timepoint(s) of evaluation of this end point: Part 1 The review of DLTs and AEs will be continuous to inform dose escalation, and then after all patients r | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: - Lenalidomide RDI after 4 cycles of treatment with belantamab mafodotin in combination with VRd - Bortezomib RDI after 4 cycles of treatment with belantamab mafodotin in combination with VRd - Cumulative administered dose of belantamab mafodotin after 4 cycles of treatment in combination with VRd - Belantamab mafodotin, total mAb, and cys-mcMMAF PK parameters, as data permit - Incidence and titers of ADAs against belantamab mafodotin Part 2: - ORR, defined as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR, sCR) - CRR, defined as the percentage of participants with a confirmed CR or better (i.e., CR, sCR) - Rate of VGPR or better, defined as the percentage of participants with a confirmed VGPR or better (i.e. VGPR, CR, sCR) - DoR, defined as the time from first documented evidence of PR or better until PD or death due to PD among participants who achieve confirmed PR or better - TTP, defined as the time from the date of randomization until the earliest date of documented PD or death due to PD - OS, defined as the time from the date of randomization until the date of death due to any cause - Sustained MRD negativity defined as the percentage of patients with MRD negativity confirmed 1 year apart - Incidence of adverse events (AEs) - Ocular findings on ophthalmic exam -Plasma concentrations of belantamab mafodotin, total mAb, and cys-mcMMAF -ncidence and titers of ADAs against belantamab mafodotin -Change from baseline in HRQOL as measured by EORTC QLQ-C30 and EORTC QLQ-MY20 symptoms (pain) domain - Changes from baseline in symptoms and related impacts as measured by PRO-CTCAE - Changes from baseline in symptoms and related impacts as measured by OSDI;Timepoint(s) of evaluation of this end point: Part 1: - Lenalidomide and bortezomib RDI endpoints: after all patients recruited in Part 1 have completed 4 cycles of treatment. - PK and ADAs endpoints: final analysis Part 2: -Ef | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Denmark, France, Germany, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Romania, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed