An open label, multicenter, phase I/II study of belantamab mafodotin in combination with Kd for the treatment of relapsed myeloma patients, refractory to lenalidomide

Prior treatment

• Participant has received prior treatment with anti-BCMA agents.
• Received plasmapheresis within 7 days prior to the first dose of study drug.
• Participant has received 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.
• Major surgery (except kyphoplasty) ≤ 4 weeks prior to initiating protocol therapy.
• Participant has 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.
• Participant has 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.
• Participant has used a systemic anti-myeloma drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
• Participant has used an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
• Prior treatment with a monoclonal antibody against MM within 30 days of receiving the first dose of study drug.

Other illness

• Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome at the time of screening.
• Participant has a 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 has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to other monoclonal antibodies.
• Participant has current corneal epithelial disease except mild punctate keratopathy.
• Participant has peripheral neuropathy or neuropathic pain grade ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
• Participant has invasive 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.
• Participant has current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
• Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect patient’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil inclusion criteria.
• Evidence of active mucosal or internal bleeding.
• Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
• Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
• Patients with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
• Patients with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%.
• History of interstitial lung disease or ongoing interstitial lung disease.
• Participant has an active infection requiring antibiotic, antiviral, or antifungal treatment
• Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction.
• Participant has known HIV infection

Lab values

• Participant evidence of cardiovascular risk including any of the following: - QTcF interval QTcF > 480 msec (the QT interval values must be corrected for heart rate by Fridericia’s formula [QTcF]) - Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (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 six months of Screening.- Class III or IV heart failure as defined by the New York Heart Association functional classification system [NYHA, 1994] - Uncontrolled hypertension, defined as an average systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg despite optimal treatment.

Other

• Use of contact lenses while participating in this study.
• Participant has meningeal involvement of multiple myeloma.
• Pregnant or breastfeeding females.
• Participant is simultaneously enrolled in other interventional clinical trial.

• Patient is, in the investigator’s opinion, willing and able to comply with the protocol requirements.
• Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 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.
• Patient has given voluntary written informed consent before performance of any study-related procedure nor part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Relapse multiple myeloma patients that have received at least 1 and no more than 3 prior lines of therapy. Induction, intensification with high-dose melphalan and stem cell transplant and maintenance is considered one line of treatment.
• Patients must be refractory to lenalidomide. Refractoriness is defined as progression while receiving lenalidomide or in the first 60 days after the last dose of lenalidomide. Refractoriness would be defined regardless of the dose of lenalidomide received, and the schedule or whether it was given alone or in combination.
• Patients can have received prior treatment with proteasome inhibitors. Patients with prior bortezomib treatment are eligible regardless of refractory status. Prior carfilzomib treatment is allowed, provided that the patients achieve at least a partial response to prior carfilzomib, and that there is a treatment free interval of at least 6 months.
• Participant must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 100mg/L (10mg/dl), with an abnormal serum FLC ratio.
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Participant must be ≥ 18 years of age.
• Participant must have adequate organ function, defined in table 6