Study of Belantamab Mafodotin as Pre- and Post-autologous Stem Cell Transplant and Maintenance for Multiple Myeloma

Study Overview
=================
Brief Summary
-----------------
This is a single-institution, single-arm, phase 2 study in which belantamab mafodotin (GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen (BCMA), will be administered to patients with multiple myeloma prior to and following high-dose melphalan and autologous stem cell transplantation (ASCT), in conjunction with standard lenalidomide maintenance. We hypothesize that administration of belantamab mafodotin as part of autologous stem cell transplant consolidation and maintenance will be safe, well tolerated, and efficacious in comparison to historical data.

Official Title
-----------------
Phase 2 Study of Belantamab Mafodotin as Pre- and Post-autologous Stem Cell Transplant Consolidation and Maintenance for Multiple Myeloma

Conditions
-----------------
Myeloma

Intervention / Treatment
-----------------
* Drug: Belantamab mafodotin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must have started therapy for active multiple myeloma within 12 months of enrollment. Subjects must have an 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 complete response (CR) or better 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. Eligible to receive lenalidomide maintenance therapy post-ASCT. Adequate bone marrow and organ function at enrollment Exclusion Criteria: Participant must not have used an investigational drug or approved systemic anti-myeloma 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 POEMS syndrome. Participants must not be pregnant or lactating. Participant 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, provided they fulfill criteria given in Section 6.1. Participant must not have evidence of cardiovascular risk 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 HBV re-activation for the duration of the study. Participant must not have 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. 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. Participant must not have evidence of active HIV infection. Participants with positive HIV serologies who are on stable active anti-retroviral therapy, have CD4 count > 200 cells/µL, 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belantamab mafodotin<br>Patients receive Belantamab mafodotin 2.5 mg/kg by intravenous infusion on day -42 relative to autologous stem cell infusion (day 0), on day +60, and every 90 days thereafter, for up to 2 years following ASCT. | Drug: Belantamab mafodotin<br>* 2.5 mg/kg IV<br>* Other names: GSK2857916;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRD (minimal residual disease) negativity rate | Percentage of participants who have achieved minimal residual disease (MRD) negativity by next-generation sequencing (NGS) at 12 months post-autologous stem cell transplant (ASCT) | 12 months post-ASCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of treatment-related adverse events | Percentage of participants who develop adverse and serious adverse events, including ocular adverse events. | through study completion, approximately 3 years | 
| Dose reductions | The percentage of participants who require reduction of the dose of belantamab mafodotin will be assessed | through study completion, approximately 3 years | 
| Dose delays | The percentage of participants who require a delay in dosing of belantamab mafodotin will be assessed | through study completion, approximately 3 years | 
| MRD Negativity Rate | Percentage of participants who have achieved minimal residual disease (MRD) negativity by next-generation sequencing (NGS) at 3 and 24 months post-autologous stem cell transplant (ASCT) | at 3 and 24 months post-ASCT | 
| Overall response rate | Percentage of participants who achieve partial response (PR) or better, as assessed by International Myeloma Working Group (IMWG) criteria. | through study completion, approximately 3 years | 
| Very good partial response (VGPR) or better rate | Percentage of participants who achieve VGPR or better, as assessed by IMWG criteria. | through study completion, approximately 3 years | 
| Complete response (CR) or better rate | Percentage of participants who achieve CR or stringent CR, as assessed by IMWG criteria. | through study completion, approximately 3 years | 
| Progression-free survival | Time from enrollment until progression of disease by IMWG criteria, or death, whichever occurs first | through study completion, approximately 3 years | 
| Overall survival | Time from enrollment until death from any cause | through study completion, approximately 3 years | 
| Stem cell yield | The number of days required to collect sufficient autologous peripheral blood stem cells to proceed to ASCT will be assessed | Following stem cell mobilization, about 6 weeks after enrollment | 
| Stem cell collection days | : The number of days required to collect sufficient autologous peripheral blood stem cells to proceed to ASCT will be assessed | Following stem cell mobilization, about 6 weeks after enrollment | 
| Hematopoietic reconstitution post-ASCT | The number of days until neutrophil and platelet recovery post-ASCT (defined as absolute neutrophil count >1000 cells/mcl and platelet count >50000 cells/mcl, respectively) will be assessed | up to 30 days post-ASCT | 
| Change from Baseline in Health-related quality of life (HRQoL) as assessed by Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) questionnaire | The FACT-MM questionnaire is a 41 item questionnaire measuring physical, social/family, emotional, and functional well-being, as well as additional concerns | baseline through study completion, approximately 3 years. |