Relapsed/Refractory Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capable of giving signed informed consent as described in Section 10.1.3 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. 2. Male or female, 18 years or older (at the time consent is obtained). 3. Confirmed diagnosis of multiple myeloma as defined by the IMWG criteria. 4. Previously treated with at least 1 prior line of multiple myeloma (MM) therapy, and must have documented disease progression during or after their most recent therapy. Note: induction + autologous stem cell transplant (ASCT) + maintenance is 1 line of therapy 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Section 10.6 of the protocol). 6. Participants with a history of ASCT are eligible for study participation provided the following eligibility criteria are met: a. ASCT was >100 days prior to initiating study treatment, and b. No active bacterial, viral, or fungal infection(s) present. 7. Must have at least ONE aspect of measurable disease, defined as one the following: a. Urine M-protein excretion =200 mg/24h, 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). 8. All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0) must be = Grade 1 at the time of enrollment, except for alopecia. 9. Adequate organ system functions as defined by the laboratory assessments listed in Table 3 of the protocol. 10. Female Participants: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 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 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 (Section 10.3 of the protocol) during the intervention period and for 4 months after the last dose of belantamab mafodotin, 3 months from the last dose of daratumumab, and 7 months from the last dose of bortezomib, whichever is longer 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. WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1. Additional requirements for pregnancy testing during and after study intervention are provided in Section 10.3 and the Schedule of Activities (SoA) of the protocol. 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. 11. Male Participants: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following from the time of first dose of study until 6 months after the last dose of belantamab mafodotin, and 4 months from the last dose of
Exclusion criteria
Exclusion criteria: 1. Intolerant to daratumumab. 2. Refractory to daratumumab or any other anti-CD38 therapy (defined as progressive disease during treatment with anti-CD38 therapy, or within 60 days of completing that treatment). 3. Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease during treatment with a bortezomib-containing regimen of 1.3 mg/m2 twice weekly, or within 60 days of completing that treatment). Note: participants with progressive disease during treatment with a weekly bortezomib regimen are allowed. 4. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. 5. Prior treatment with anti-BCMA therapy. 6. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs, or treatment with an investigational agent or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter. 7. Plasmapheresis within 7 days prior to the first dose of study drug. 8. Has received radiotherapy to a large pelvic area (check with sponsor). Bridging radiotherapy otherwise is allowed. NOTE: Disease assessment should be repeated if RT is done prior to first dose of study drug within screening window. 9. Prior allogenic stem cell transplant. NOTE – Participants who have undergone syngeneic transplant will be allowed, only if no history of GvHD. 10. Any major surgery within 4 weeks prior to the first dose of study drug. Exception allowed for bone stabilizing surgery after consultation with medical monitor. 11. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil criteria given in Table 3 of the protocol. 12. 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. 13. Evidence of active mucosal or internal bleeding. 14. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria. 15. Previous or concurrent malignancies other than multiple myeloma, unless the second malignancy 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. 16. Evidence of cardiovascular risk including any of the following: a. Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including second degree (Mobitz Type II) or third degree atrioventricular (AV) block. b. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening. c. Class III or IV heart failure as defined by the New York Heart Association functional classification system (Sect
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of belantamab mafodotin in combination with bortezomib and dexamethasone (bor/dex) with that of daratumumab in combination with bor/dex in participants with RRMM;Secondary Objective: - To compare the efficacy of belantamab mafodotin in combination with bor/dex with that of daratumumab in combination with bor/dex in participants with RRMM - (Key secondary objective) -To further assess the efficacy of belantamab mafodotin in combination with bor/dex with that of daratumumab in combination with bor/dex in terms of other efficacy outcomes in participants with RRMM -To evaluate the safety and tolerability of belantamab mafodotin when administered in combination with bor/dex -To further describe the exposure to belantamab mafodotin when administered in combination with bor/dex -To assess anti-drug antibodies (ADAs) against belantamab mafodotin -To evaluate the safety and tolerability of belantamab mafodotin based on self-reported symptomatic adverse effects when administered in combination with bor/dex -To evaluate and compare changes in symptoms and health-related quality of life (HRQOL);Primary end point(s): Progression-Free Survival (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: Up to approximately 34 months from the time when the first participant is randomized (progression-free survival final analysis) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Minimal Residual (MRD) negativity rate, defined as the percentage of participants who are MRD negative by next-generation sequencing (NGS) - (key secondary endpoint) -Complete Response Rate (CRR), defined as the percentage of participants with a confirmed complete response (CR) or better (i.e., CR, stringent complete response (sCR)) -Overall Response Rate (ORR), defined as the percentage of participants with a confirmed partial response (PR) or better (i.e., PR, VGPR, CR, sCR) -Duration of Response (DoR), defined as the time from first documented evidence of PR or better until progressive disease (PD) or death due to PD among participants who achieve confirmed PR or better -Time to Response (TTR), defined as the time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better -Time to Progression (TTP), defined as the time from the date of randomization until the earliest date of documented PD or death due to PD -Overall Survival (OS), defined as the time from the date of randomization until the date of death due to any cause -PFS2, defined as time from randomization to disease progression after initiation of new anti-cancer therapy or death from any cause, whichever is earlier. If disease progression after new anti-cancer therapy cannot be measured, a PFS event is defined as the date of discontinuation of new anti-cancer therapy, or death from any cause, whichever is earlier -Minimal Residual Disease (MRD) negativity rate, defined as the percentage of participants who are MRD negative by next-generation sequencing (NGS) - Incidence of adverse events (AEs) and changes in laboratory parameters - Ocular findings on ophthalmic exam - Plasma concentrations of belantamab mafodotin, total monoclonal antibody (mAb), and cys-mcMMAF - Incidence and titers of anti-drug antibodies (ADAs) against belantamab mafodotin - Changes from baseline in symptoms | — |
Countries
Australia, Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed