Belantamab Mafodotin as Pre- and Post- Autologous Stem Cell Transplant Consolidation and Maintenance for the Treatment of Multiple Myeloma

Inclusion Criteria

• Subjects must be able to understand the study procedures and have signed written, informed consent
• Subjects must be >= 18 years of age at enrollment
• Subjects must have started therapy for active multiple myeloma within 12 months of enrollment
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Have received no more than 2 prior lines of induction therapy (induction regimen not specified by protocol), with no prior progressive disease by International Myeloma Working Group (IMWG) criteria
• Must be in at least a partial response (PR) but not in a stringent complete response (sCR) after at least 4 cycles of induction therapy, per IMWG consensus criteria
• Eligible by institutional criteria to receive melphalan at a dose of 200 mg/m2, including: * Left ventricular ejection fraction >= 45% as determined by transthoracic echocardiography or multigated acquisition scan (MUGA) scan. * Adequate pulmonary function with forced expiratory volume at 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and diffusion capacity of the lung for carbon monoxide (DLCO) (after appropriate adjustment for lung volume and hemoglobin concentration) >= 40% of predicted values.
• Eligible to receive lenalidomide maintenance therapy post-ASCT
• Absolute neutrophil count (ANC) >= 1,000/uL
• Hemoglobin >= 8.0 g/dL
• Platelets >= 75,000/uL
• Estimated (using Cockcroft-Gault) or measured creatinine clearance < 50 mL/min
• Spot urine albumin/creatinine ratio < 500 mg/g
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN)
• Total bilirubin < 1.5 x ULN (isolated bilirubin >= 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%)
• Female participants: contraceptive use 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), 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 at least 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 study intervention.
• A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of belantamab mafodotin. 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 a nearly undetected pregnancy. Non-childbearing potential is defined as follows (by other than medical reasons): * >= 45 years of age and has not had menses for > 1 year * Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation * Post-hysterectomy, post-bilateral oophorectomy, or post-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.
• Male participants: contraceptive use 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 during belantamab mafodotin treatment and for 6 months after the last dose of belantamab mafodotin 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 woman of childbearing potential (including pregnant females).
• All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 5.0) must be =< grade 1 at the time of enrolment except for alopecia
• Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

Exclusion Criteria

• Participant must not have used an investigational drug or approved systemic antimyeloma therapy (including systemic steroids) within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug
• Participant must not have received treatment with a monoclonal antibody within 28 days of receiving the first dose of study drug
• Participant must not be simultaneously enrolled in any interventional clinical trial
• Participant must not have amyloidosis or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
• Participants must not be pregnant or lactating. Female subjects of reproductive potential (women who have reached menarche and who have had menses within the preceding 24 months or have not undergone hysterectomy or bilateral oophorectomy) must have a negative serum pregnancy test performed at the time of screening
• Participants must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, severe hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis * Note: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria
• Participant must not have any evidence of active mucosal or internal bleeding
• History of an active renal condition (infection, requirement for dialysis or any other condition that could affect subject’s safety). Subjects with isolated proteinuria resulting from MM are eligible
• Participant must not have evidence of cardiovascular risk including any of the following: * Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block * History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three (3) months of screening. * Uncontrolled hypertension * Class III or IV heart failure as defined by the New York Heart Association functional classification system
• Participants must not have any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures
• Participant must not have invasive malignancies other than disease under study, unless the second malignancy has been definitively treated or has been medically stable for at least 2 years and, in the opinion of the principal investigator, will not affect the evaluation of the effects of clinical trial treatment
• Participants must not have an active infection requiring antibiotic treatment
• Any major surgery within the last 4 weeks prior to enrollment
• Participant must not have current corneal epithelial disease except mild changes in corneal epithelium
• Participant must not have known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment
• Participant must not have evidence for active hepatitis B infection (i.e. positive hepatitis B surface antigen or nucleic acid-based testing) at screening or within 3 months prior to first dose of belantamab mafodotin. Subjects with positive testing for hepatitis B core antibody but no evidence for active infection by nucleic acid-based testing may enroll if they agree to hepatitis B prophylactic therapy and monitoring for hepatitis B virus (HBV) reactivation for the duration of the study
• Participant must not have positive hepatitis C antibody test result or positive hepatitis C ribonucleic Acid (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 C RNA testing is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing
• Participants must not have evidence of active human immunodeficiency virus (HIV infection) (positive serology with appropriate positive confirmatory testing, such as nucleic acid-based testing). Participants with positive HIV serologies who are on stable active anti-retroviral therapy, have CD4 count > 200 cells/uL and have no detectable HIV virus by nucleic acid-based testing at screening or within 3 months prior to first dose of study drug may be eligible after discussion with medical director and/or principal investigator