A Safety and MORAb-028 Dose Determination Study in Subjects With Metastatic Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether therapy with MORAb-028 is safe, effective, and to determine the appropriate dose of MORAb-028 in the treatment of metastatic melanoma.

Detailed Description
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Melanoma is a serious form of skin cancer. If untreated, the melanoma can spread beyond the original affected tissue and invade distant tissue and organs. Treatment for metastatic melanoma includes medical treatments (chemotherapy or immunotherapy), surgery, or radiation therapy. MORAb-028 is a recombinant human immunoglobulin M (IgM) monoclonal antibody that recognizes a cell surface diacyl ganglioside named disialoganglioside (GD2). GD2 is overexpressed in tumors of neuro-ectodermal origin such as melanomas, neuroblastomas, small-cell lung carcinomas, and many sarcomas, while absent in most normal tissues. GD2 expression has been demonstrated in human melanoma and small cell lung cancer by thin layer chromatography and radiolabeled anti-GD2 antibody detection. It is hypothesized that one mode of action of MORAb-028 is complement-dependent cytotoxicity. Complement-dependent cytotoxicity is a mechanism for killing tumor cells in which an antibody bound to the target cell surface fixes complement, which results in assembly of the complement membrane attack complex that punches holes in the target cell membrane resulting in subsequent cell lysis. IgMs strongly bind to C1Q and robustly activate complement-dependent cytotoxicity. MORAb-028 is being developed as a potential therapy for GD2-positive tumors.

Official Title
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A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Radiologic Distribution of Ascending Single-Dose Radiolabeled MORAb-028 in Subjects With Metastatic Melanoma

Conditions
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Metastatic Melanoma, Malignant Metastatic Melanoma, Advanced Melanoma, Melanoma

Intervention / Treatment
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* Drug: MORAb-028


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Measurable metastatic melanoma that has failed standard therapy Males and females greater than or equal to 18 years of age Life expectancy of greater than or equal to 3 months Exclusion Criteria: Significant cardiovascular impairment Clinically significant illness, medical condition, surgical history, or laboratory abnormality that could affect the safety of the subject or negatively impact the study results Chemotherapy, radiotherapy, or immunotherapy within 3 weeks prior to administration to MORAb-028

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>MORAb-028 0.1 mg/kg intravenous | Drug: MORAb-028<br>* Cohort 1: 0.1 mg/kg IV on study day 1 only Cohort 2: 0.2 mg/kg IV on study day 1 only Cohort 3: 0.5 mg/kg IV on study day 1 only Cohort 4: 1.0 mg/kg IV on study day 1 only<br>|
| Experimental: Cohort 2<br>MORAb-028 0.2 mg/kg intravenous | Drug: MORAb-028<br>* Cohort 1: 0.1 mg/kg IV on study day 1 only Cohort 2: 0.2 mg/kg IV on study day 1 only Cohort 3: 0.5 mg/kg IV on study day 1 only Cohort 4: 1.0 mg/kg IV on study day 1 only<br>|
| Experimental: Cohort 3<br>MORAb-028 0.5 mg/kg intravenous | Drug: MORAb-028<br>* Cohort 1: 0.1 mg/kg IV on study day 1 only Cohort 2: 0.2 mg/kg IV on study day 1 only Cohort 3: 0.5 mg/kg IV on study day 1 only Cohort 4: 1.0 mg/kg IV on study day 1 only<br>|
| Experimental: Cohort 4<br>MORAb-028 1.0 mg/kg intravenous | Drug: MORAb-028<br>* Cohort 1: 0.1 mg/kg IV on study day 1 only Cohort 2: 0.2 mg/kg IV on study day 1 only Cohort 3: 0.5 mg/kg IV on study day 1 only Cohort 4: 1.0 mg/kg IV on study day 1 only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of single dose radio labeled MORAb-028 in subjects with metastatic melanoma |  | Daily for 7 days followed by weekly for 2 weeks, then biweekly for 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiologic distribution of a single i.v. infusion of MORAb-028 |  | Daily for 1 week post study drug administration | 
| Pharmacokinetic parameters of labeled and unlabeled MORAb-028 |  | Daily for 7 days followed by weekly for 2 weeks, then biweekly for 4 weeks | 
| The incidence of human antihuman antibody formation |  | Week 2 and Week 8 |