Critères d'inclusion : 1. Participant must be 18 years of age inclusiveor older, at the time of signing the informed consent.
2. Participants who have histologically or cytologically confirmed diagnosis of MM,as defined by the International Myeloma Working Group(IMWG, [Rajkumar, 2014]).
3. Participants who have been treated with at least 3 prior lines of prior anti-myeloma treatments including an IMID (eg. lenalidomide), a proteasome inhibitor (eg. bortezomib) and an anti-CD38 monoclonal antibody. Lines of therapy are defined by consensus panel of the International Myeloma Workshop [Rajkumar, 2011a].
4. 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 prior to screening
b. no active infection(s)
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
6. Measurable disease defined as at least 1 of the following:
• Serum M-protein ≥0.5 g/dL (≥5 g/L)
• Urine M-protein ≥200 mg/24 hours
• Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
7. Have organ system functions as defined by the laboratory assessments in Table 13.
8. All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events [NCI -CTCAE], version 5.0, 2017) must be Grade ≤1 at the time of screening except for alopecia (any grade), neuropathy (Grade ≤2), or endocrinopathy managed with replacement therapy (any grade).
9. Male or female
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see Appendix 7 for further details).
a. Male Participants:
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in the clinical studies.
Male participants are eligible to participate if they agree to the following during the intervention period and for at least 140 days after the last dose of study intervention to allow for clearance of any altered sperm:
Refrain from donating sperm
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
• Must agree to use contraception/barrier as detailed below
• Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant
b. 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 one of the following conditions applies:
• Is not a woman of childbearing potential (WOCBP)
• 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 Appendix 7 during the intervention period and for at least 120 days after the last dose of study intervention 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.
• A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 72 hours before the first dose of study intervention.
• 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
10. Capable of giving signed written informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Critères de non-inclusion : Medical Conditions
1. Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes’ (POEMS) syndrome, active plasma cell leukemia at the time of screening.
2. 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 with study procedures.
3. Current corneal epithelial disease except mild punctate keratopathy
4. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria.
5. Malignancies other than disease under study are excluded, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM).
Participants with curatively treated non-melanoma skin cancer are not excluded.
6. Evidence of cardiovascular risk including any of the following:
a. QTcF interval ≥480 msecs (the QT interval values must be corrected for heart rate by Fridericia’s formula [QTcF])
b. Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobiz Type II) or 3rd degree atrioventricular (AV) block.
c. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting or bypass grafting, all within three months of Screening.
d.Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
e. Uncontrolled hypertension
f. Recent (within the past 6 months) history of symptomatic pericarditis.
7. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK’916 (belantamab mafodotin) or any of the components of the study treatment. History of severe hypersensitivity to other mAbs.
8. Active infection requiring antibiotic, antiviral, or antifungal treatment.
9. Known HIV infection.
10. Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
11. 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
12. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
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. Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
13. Patients who have received prior therapy with GSK’916 (belantamab mafodotin).
14. Other monoclonal antibodies within 30 days orsystemic anti-myeloma therapy within <14 days of first dose of study drug.
15. Prior radiotherapy within 2 weeks of start of study therapy. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
16. Plasmapheresis within 7 days prior to the first dose of study drug
17. Prior allogeneic transplant is prohibited
18. Patients who have received prior CAR-T therapy with lymphodepletion with chemotherapy within 3 months of screening.
19. Any major surgery (other than bone-stabilizing surgery) within 30 days of screening.
20. 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.
For 'Other Exclusions' please refer to the protocol.