The Primary Objective of the Trial is to Evaluate the Effect of the Addition of Belantamab Mafodotin to Standard of Care Therapy on the Titres of Serum Anti-dsDNA Antibodies in Patients With Previously Treated SLE.

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.

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.

What this study is about