Multiple myeloma = cancer of blood cells in the bone marrow MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Participant must be 18 years of age inclusive at the time of signing the Informed Consent Form (ICF). Type of Participant and Disease Characteristics 2. Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (see Section 10.8). 3. Participant has a histologically- or cytologically-confirmed diagnosis of MM as defined by IMWG criteria [Rajkumar, 2016], and a. Has undergone stem cell transplant or is considered transplant ineligible, and b. Has failed at least 3 prior lines of anti-MM therapies, including an anti-CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory to an immunomodulatory agent (e.g., lenalidomide, pomalidomide) and a proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib). 4. Participant has measurable disease with at least one of the following criteria: a. Serum M protein =0.5 g/dL (=5 g/L), or b. Urine M protein =200 mg/24h, or c. Serum free light chain (FLC) assay: Involved FLC level =5 mg/dL (=50 mg/L) and an abnormal serum FLC ratio (1.65), or d. Non-irradiated plasmacytoma with =1 measurable lesion that has a single diameter of =2 cm 5. Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: a. Transplant was >100 days before study enrollment, and b. Participant has no active infection(s), and c. Participant meets the remainder of the eligibility criteria outlined in this protocol. 6. All prior treatment-related toxicities (defined by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] Version 5.0) must be Grade =1 at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy. 7. Life expectancy of at least 6 months, in the opinion of the investigator. Sex and Contraceptive/Barrier Requirements 8. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Female Participants A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions apply: • Is not a woman of childbearing potential (WOCBP) as defined in Section 10.9, 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 (as described in Section 10.9) during the treatment period and for at least 4 months after the last dose of study treatment 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 treatment. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose (Cycle 1 Day 1) of study treatment (see Section 8.2.7). Additional requirements for pregnancy testing during and after study treatment are provided in Section 8.2.7 and the Schedule of Activities (SoA) (Section 1.3). 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. b. Male Participants Contraceptive use by men should be c
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Participant has symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes), or active plasma cell leukemia at the time of screening. 2. Participant currently has corneal epithelial disease, except nonconfluent superficial punctate keratitis (SPK). 3. Participant has evidence of active mucosal or internal bleeding. 4. Participant has presence of an 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 fulfill adequate organ function inclusion criteria (Exclusion Criteria 24). 5. Participant has any serious and/or unstable pre-existing medical condition, psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with the participant’s safety, obtaining informed consent, or compliance with the study procedures. 6. Participant has malignancies other than the disease under study are excluded, except for any other malignancy from which the participant has been disease-free for >2 years and, in the opinion of the principal investigator and GSK medical director, will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy (MM). Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction. 7. Participant has evidence of cardiovascular risk including any of the following criteria: a. Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities including second degree (Mobitz Type II) or third degree atrioventricular block, or b. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting =3 months before screening, or c. Class III or IV heart failure as defined by the New York Heart Association functional classification system (see Section 10.11). d. Uncontrolled hypertension. 8. Participant is a pregnant or lactating female. 9. Participant has an active infection requiring antibiotic, antiviral, or antifungal therapy. 10. Participant has known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria: a. Established anti-retroviral therapy (ART) for =4 weeks and HIV viral load <400 copies/mL, and b. CD4+ T cell (CD4+) counts =350 cells/µL, and c. No history of acquired immunodeficiency syndrome-defining opportunistic infections within the last 12 months. Liver Safety 11. Participants with hepatitis B virus (HBV) will be excluded unless the criteria in Table 5 can be met.( please refer to the protocol section 5.2) 12. Participants with a positive hepatitis C antibody test result or a positive hepatitis C virus (HCV) ribonucleic acid (RNA) test result at screening or =3 months before the first dose of study treatment will be excluded unless the participant can meet the following criteria: a. Negative HCV RNA test result b. Successful antiviral therapy (usually 8 weeks duration), followed by a negative HCV RNA test result after a washout period of =4 weeks. 13. Participant has cirrhosis or current unstable liver or biliary disease per investigator assessment, defined by the presence of as
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the ocular AEs associated with single-agent belantamab mafodotin using alternative dosing regimens in participants with RRMM in Arms B to D compared to Arm A;Secondary Objective: - To further evaluate the ocular safety and tolerability of single-agent belantamab mafodotin in all arms - To evaluate the efficacy of single-agent belantamab mafodotin in all arms - To evaluate the overall safety and tolerability of single-agent belantamab mafodotin in all arms - To assess the pharmacokinetics of single-agent belantamab mafodotin in all arms - To assess anti-drug antibodies against single-agent belantamab mafodotin in all arms;Primary end point(s): Incidence rate of Grade =2 ocular AEs according to the KVA scale;Timepoint(s) of evaluation of this end point: From when the first participant initiated treatment until 9 months after the last participant is randomized into Arms A to D. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: From when the first participant initiated treatment until 9 months after the last participant is randomized into Arms A to D.;Secondary end point(s): - Cumulative event rate of ocular AEs to Week 16 (KVA scale) - Incidence rate of ocular AEs by grade (KVA scale) - Exposure-adjusted incidence rate of ocular AEs by grade (KVA scale) - Median duration of dose delay - Percentage of participants requiring dose reductions, dose delays, and study treatment - discontinuation due to ocular AEs (KVA scale) - Cumulative incidence of ocular AEs by grade (KVA scale) - Toxicity Index by assessment/visit - Duration of ocular AEs (KVA scale) - Percentage of time on study with ocular AEs (KVA scale) - Change in BCVA (?logMAR) - ORR, defined as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR, and sCR)* - Percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, and sCR)* - TTR is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better)* - DoR in responders, defined as the time from first documented evidence of PR or better until PD or death due to PD* - TTP, defined as the time from randomization until the earliest date of documented PD or death due to PD* - PFS, defined as the time from randomization until the earliest date of documented PD or death due to any cause* - OS, defined as the time from randomization until the date of death due to any cause - Instance of AEs (including ocular AEs) (CTCAE Version 5.0) and changes in laboratory parameters - Percentage of participants requiring dose reductions, dose delays, and study treatment - Discontinuation due to any AEs (CTCAE Version 5.0) - Plasma belantamab mafodotin pharmacokinetic parameters, as data permit - Incidence and titers of ADAs against belantamab mafodotin and total monoclonal antibody plasma co | — |
Countries
Argentina, Australia, Brazil, Canada, France, Germany, Greece, India, Ireland, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactCentro de Información
GlaxoSmithKline
Outcome results
None listed