A Phase 1 With Extension Cohort, Single Arm, Single Center, Open Label Trial of Belantamab Mafodotin for the Treatment of High-Risk Smoldering Multiple Myeloma

* Evidence of myeloma defining events or biomarkers of malignancy due to underlying plasma cell proliferative disorder meeting at least one of the following:

* Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal or \> 2.75 mmol/L (\> 11 mg/dL)

* Renal Insufficiency: creatinine clearance \< 40 ml/min or serum creatinine \> 2 mg/dL

* Anemia: hemoglobin value more than 2 g/dL \< normal reference

* Bone lesions: one or more osteolytic lesions on skeletal radiography, computerized tomography (CT) or 2-deoxy-2\[F-18\] fluoro-D-glucose positron emission tomography CT (PET-CT).

* Clonal bone marrow plasma cell percentage ≥ 60%

* Involved: uninvolved serum free light chain ratio ≥100 measured by Freelite assay (The Binding Site Group, Birmingham, UK)

* \>1 focal lesions on MRI studies (each focal lesion must be 5 mm or more in size)

* Bisphosphonates are permitted, including pamidronate, zoledronic acid, alendronate, ibandronate, risedronate.

* Treatment with corticosteroids is not permitted, unless the patient is on a stable chronic dose of inhaled steroids to treat respiratory diseases or on stable chronic steroid replacement therapy for endocrinology disorders. Steroids may be used treat infusion related reactions. Inhaled, intranasal, and topical ophthalmic steroids are not prohibited.

* Radiotherapy is not permitted.

* Prior or concurrent treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of smoldering multiple myeloma

* Plasma cell leukemia

* Pregnant or lactating females. It is not known whether belantamab mafodotin is excreted in human milk. The effect of belantamab mafodotin of newborns/infants is unknown. Women should be advised to discontinue breast-feeding prior to initiating treatment with belantamab mafodotin and for at least 70 days after the last dose. These potential risks may also apply to other agents used in this study.

* Active hepatitis B or C infection

* Known HIV infection

* Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin

* Concurrent treatment with other anti-cancer therapy is not permitted

* Has significant cardiovascular disease with:

* NYHA Class III or IV symptoms,

* uncontrolled hypertension

* hypertrophic cardiomyopathy restrictive cardiomyopathy, or myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months prior to enrollment

* evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block as determined by history and physical examination.

* Uncontrolled intercurrent illness including but not limited to active infection requiring treatment or psychiatric illness/social situations that would compromise compliance with study requirements

* Contraindication to any concomitant medication, including pre-medications or hydration given prior to therapy

* Major surgery within 1 month prior to enrollment

* Previous or concurrent malignancies other than disease under study, unless the second malignancy has been medically stable for at least 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of clinical trial treatments on the currently targeted malignancy. Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction.

* Presence of active renal condition (infection, requirement for dialysis, or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting are eligible, provided they fulfil renal criteria provided above.

* Any evidence of active mucosal or internal bleeding

* Received prior treatment with a monoclonal antibody within 30 days of receiving the first dose of belantamab mafodotin

* Cirrhosis or current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, 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

* Current corneal epithelial disease except mild changes in corneal epithelium

* Use of contact lenses while participating in this study, except at the direction of the study MD/OD

* Severe dry eye patients and monocular patients are excluded

What this study is about