Inclusion Criteria
1. Diagnosis of SLE according to the 2019 EULAR/ACR SLE classification criteria.
2. Age between 18 and 60 years.
3. Have a body mass index (BMI) between 18 and 32 kg/m² (BMI = weight/height2), inclusive, and a body weight of no less than 35 kg.
4. Have a positive anti-dsDNA test (enzyme-linked immunosorbent assay \[ELISA\]).
5. Active disease, defined by a SLE Disease Activity Index (Safety of Estrogens in Systemic Lupus Erythematosus National Assessment \[SELENA\] SLEDAI score≥ 6, including clinical SLEDAI ≥ 4 (please refer to APPENDIX 5 - SELENA SLEDAI SCORE).
6. Demonstrate moderate to severe disease based on SLEDAI-2K score ≥ 6 observed at screening (please refer to APPENDIX 6 - SLEDAI-2K SCORE)
7. Failure to, or lack of tolerability of, at least one previous state-of-the-art immunosuppressive drug (does not account for GC).
8. Patients with either extra-renal disease or patients with kidney involvement (LN) are eligible. LN patients should be class III, IV, or V (please refer to APPENDIX 8 - LUPUS NEPHRITIS CLASSIFICATION).
9. Adequate organ system function as defined by the below laboratory assessments. Hematologic
1. Absolute neutrophil count (ANC) ≥1.5 X 109/L; granulocyte colony stimulating factor use within the past 14 days is NOT permitted.
2. Hemoglobin ≥8.0 g/dL; transfusions within the past 14 days are NOT permitted. Erythropoietin use is allowed.
Hepatic
1. Total bilirubin ≤1.5xUpper limit of normal (ULN) (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
2. Alanine aminotransferase (ALT) ≤ 2.5xULN. Renal
a. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2; calculated using the Modified Diet in Renal Disease formula (please refer to APPENDIX 9 - MODIFIED DIET IN RENAL DISEASE (MDRD) FORMULA).
10. Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials.
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) defined as follows:
1. ≥45 years of age and has not had menses for \>1 year with no other cause.
2. Any participants who have been amenorrhoeic for \>1year but \<2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation.
3. Post-hysterectomy, post-bilateral oophorectomy, or post-bilateral tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
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 during the intervention period and for 4 months after the last dose of belantamab mafodotin 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 trial intervention (please refer to APPENDIX 2 - Contraception Guidance).
* WOCBP must have a negative highly sensitive serum pregnancy test at screening within 10 to 14 days prior to the start of treatment and the second pregnancy test must be performed within 24 hours prior to the start of treatment and agree to use a highly effective method of contraception during the trial and for 4 months after the last dose of belantamab mafodotin.
Additional requirements for pregnancy testing during and after trial intervention are provided in 1.3 Schedule of Activities The investigator is responsible for a review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.
11. Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials:
Male participants are eligible to participate if they agree to the following during the intervention period and until 6 months after the last dose of belantamab mafodotin, whichever is longer, to allow for clearance of any altered sperm.
• Refrain from donating sperm
PLUS, either:
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR
* Must agree to use contraception/barrier as detailed below:
Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \<1% per year as when having sexual intercourse with a WOCBP (including pregnant females).
12. Participants must be able to understand the trial procedures and agree to participate in the trial by providing written informed consent.
5.3 Exclusion Criteria
Participants are excluded from the trial if any of the following criteria apply:
1. Severe kidney (rapidly progressive class III or IV glomerulonephritis) or neuropsychiatric SLE (e.g., optic neuritis, transverse myelitis, psychosis, uncontrolled seizures), pulmonary haemorrhage, myocarditis) that is likely to warrant escalation in therapy beyond permitted background medications. Subjects requiring renal haemodialysis or peritoneal dialysis are also excluded.
2. Active infection, requiring treatment, and/or serious infection (e.g. sepsis, pneumonia, or pyelonephritis), or history of hospitalization or IV antibiotics receipt for a serious infection during the 3 months prior to consent.
3. Latent or active tuberculosis
4. Major surgery, (e.g. requiring general anesthesia) within 3 months before screening.
NOTE 1: The participant must be clinically stable following a major surgery to be entered in the trial.
NOTE 2: Major surgery shall be defined based on the Investigator's judgment according to the extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcome s.
5. Acute illness, including a common cold, within 2 weeks prior to first trial treatment or has had a major illness or hospitalization within 3 months prior to consent.
6. Other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis, psoriatic arthritis.
7. History of any clinically significant medical illness, or medical disorders the investigator considers significant should exclude the participant, including (but not limited to), hematological disease, immune deficiency states, respiratory disease, cardiovascular disease (including poor peripheral venous access), hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease.
8. Chronic liver disease. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, 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.
9. Participant has received B cell depleting therapy within 12 months prior to first administration of the trial agent (e.g. RTX, ocrelizumab or obinutuzumab),
10. Participant has received a therapy that inhibits B-cell activating factor (BAFF) (i.e. belimumab) within 2 months prior to first administration of the trial agent.
11. Participant has received prior experimental immunosuppressive biologic therapy for lupus (other than that described as allowed), less than 5 half-lives or 6 months, whichever is longer prior to first administration of the trial agent.
12. Participant has received oral or IV cyclophosphamide within 2 months prior to first administration of the trial agent.
13. Participant has been previously exposed to another anti-BCMA agent.
14. Participant is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]) at screening or within 3 months prior to first dose of trial treatment.
NOTE 1: Participants with resolved infection (i.e., participants who are positive for antibodies to hepatitis B core antigen \[anti-HBc\] or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR). Those who are PCR positive will be excluded.
NOTE 2: Presence of anti-HBs indicating previous vaccination will not constitute an exclusion criterion.
NOTE 3: Participants with hepatitis D virus (HDV) co-infection will be excluded. Participants with known or suspected HDV co-infection, including positive anti-HDV antibody and/or positive HDV RNA test, are not eligible for the study.
15. Participant is seropositive for hepatitis C at screening or within 3 months prior to first dose of trial 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.
16. Known HIV infection unless the participant can meet all of the following criteria:
1. Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load \<400 copies/mL
2. CD4+ T-cell (CD4+) counts ≥350 cells/μL
3. No history of AIDS-defining opportunistic infections within the last 12 months NOTE: Consideration must be given to ART and prophylactic antimicrobials that may have a drug-drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products as relevant.
17. Presence of active kidney condition (infection, requirement for dialysis, or any other significant condition that could affect participant's safety).
18. Any serious and/or unstable pre-existing medical or psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent, or compliance to the trial procedures.
19. Participant must not have received a live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.
20. Current corneal epithelial disease except mild punctate keratopathy. NOTE: Participants with mild punctate keratopathy are allowed. Mild (Grade 1) punctuate keratopathy is characterized by the appearance of only a few, if any, microcyst-like epithelial changes, as identified in the slit-lamp examination, with a low density (non-confluent), and predominantly (≥80%) located in the periphery of the cornea.
21. Known intolerance or immediate or delayed hypersensitivity reaction or idiosyncratic reaction to: drugs chemically related to belantamab mafodotin, or any of the components of the trial treatment; or infused protein products, sucrose, histidine, and polysorbate 80.
22. Evidence of active mucosal or internal bleeding.
23. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. NOTE: Investigators should ensure that all trial enrolment criteria have been met at screening. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of trial treatment is given such that he or she no longer meets all eligibility criteria, then the participant should be excluded from participation in the trial and should be considered screening failure.
