A Study to Evaluate the Safety and Efficacy of MGD013 in Patients With Melanoma

Study Overview
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Brief Summary
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This is an open-label, multi-cohort, multi-center Phase I clinical trial to evaluate the efficacy and safety of MGD013 in ① Cohort 1: patients with unresectable, recurrent or metastatic melanoma who have failed prior immune checkpoint inhibitor therapy; ② Cohort 2: patients with untreated, unresectable recurrent or metastatic, mucosal or acral lentiginous melanoma.

Detailed Description
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The study is conducted in two parts for both Cohort 1 and Cohort 2. Part I: Safety evaluation and efficacy exploration for MGD013. Part II: Efficacy expansion based on results from Part I to further evaluate the efficacy effect of MGD013.

Official Title
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An Open-label, Multi-cohort, Multi-center Phase I Study Evaluating the Efficacy and Safety of MGD013 in Patients With Unresectable, Recurrent or Metastatic Malignant Melanoma

Conditions
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Unresectable, Recurrent or Metastatic Melanoma, Untreated Mucosal or Acral Lentiginous Melanoma

Intervention / Treatment
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* Drug: MGD013


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary and able to provide signed informed consent form Male or female aged ≥ 18 years Patient can comply with protocol requirements as assessed by the investigator Eastern Cooperative Oncology Group (ECOG) performance status score of 0, or 1 Histologically confirmed unresectable recurrent or metastatic melanoma: Cohort 1: The pathological type is cutaneous or acral lentiginous, or unknown origin. Progressive or recurrent disease on at least one prior line of systemic therapies. In addition, prior systemic therapies must include one line of anti-PD-(L)1 and/or anti-CTLA-4 immune checkpoint inhibitors. Patients with BRAF-mutated or KIT-mutated/amplified melanoma, and prior treatment with vemurafenib or imatinib is not mandatory; Cohort 2: Histologically confirmed pathological type is acral lentiginous or mucosal. No prior systemic therapy for recurrent or metastatic disease. Patients with at least one measurable lesion according to irRECIST; assessed by investigator per irRECIST criteria to establish a baseline tumor assessment, and should be performed within 28 days prior to the first dose. Exclusion Criteria: The pathological type of patient is: Cohort 1: Mucosal melanoma; uveal melanoma; Cohort 2: Cutaneous melanoma; uveal melanoma; melanoma of unknown origin; known BRAF mutation or KIT mutation/amplification. Central nervous system metastases with clinical symptoms. Patients with prior central nervous system metastases who have received local therapy, have stable disease for ≥ 4 weeks, and meet the following criteria can be enrolled: No treatment for central nervous system metastases during the screening period (e.g., surgery, radiotherapy, mannitol, corticosteroid therapy-prednisolone > 10 mg per day or equivalent dose) No progression of central nervous system lesions on MRI or CT within 14 days prior to start of study treatment No meningeal metastasis or notochord compression Subjects with a history of symptomatic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired pulmonary function or may interfere with the detection and treatment of suspected drug-related pulmonary adverse reactions; Prior treatment with any antibody/drug targeting the regulation of T cell function (immune checkpoint) (e.g., anti-LAG-3, anti-0X-40, anti-CD137, anti-TIM-3, anti-TIGIT, IDO) Patients who have previously received immune checkpoint inhibitors (e.g., anti-PD-(L)1, anti-CTLA-4 antibody) are not included if they experience any of the following immune checkpoint-related adverse events, regardless of recovery: ≥ Grade 3 ocular adverse events Grade 4 liver function abnormalities Grade ≥ 3 neurologic adverse reactions ≥ Grade 3 colitis ≥ Grade 3 renal adverse reactions ≥ Grade 3 pneumonitis

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: Parallel Assignment
Interventional Model Description: ① Cohort 1: patients with unresectable, recurrent or metastatic melanoma who have failed prior immune checkpoint inhibitor therapy; ② Cohort 2: patients with untreated, unresectable recurrent or metastatic, mucosal or acral lentiginous melanoma.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unresectable, recurrent or metastatic melanoma<br>Cohort1: patients with unresectable, recurrent or metastatic melanoma who have failed prior immune checkpoint inhibitor therapy | Drug: MGD013<br>* A fixed dose of MGD013 600mg IV Q2W will be administered to subjects<br>|
| Experimental: Untreated mucosal or acral lentiginous melanoma<br>Cohort2: patients with untreated, unresectable recurrent or metastatic, mucosal or acral lentiginous melanoma | Drug: MGD013<br>* A fixed dose of MGD013 600mg IV Q2W will be administered to subjects<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective Response Rate (ORR) is defined as the proportion of patients with a best response of CR or PR in enrolled patients, which is assessed by Independent Review Committee (IRC) per RECIST v1.1 | Approximately 12 months after dosed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective Response Rate (ORR) as assessed by Investigator per RECIST v1.1 | Approximately 12 months after dosed | 
| Objective Response Rate (ORR) | Objective Response Rate (ORR) as assessed by Investigator and IRC per irRECIST. | Approximately 12 months after dosed | 
| Overall Survival (OS) | Overall Survival (OS) is defined as the time from patient enrollment to death due to any cause | Approximately 24 months | 
| Progression-free Survival (PFS) | Progression-free Survival (PFS) is defined as the time from patient enrollment to tumor progression or death due to any cause. Progression is assessed per RECIST 1.1 and irRECIST criteria, respectively | Approximately 12 months after dosed | 
| Disease Control Rate (DCR) | Disease Control Rate (DCR) is defined as the time from patient enrollment to tumor progression or death due to any cause. The tumor progression is assessed per RECIST 1.1 and irRECIST criteria, respectively | Approximately 12 months after dosed | 
| Duration of Response (DoR) | Duration of Response (DoR) is defined as the time from radiographic response to disease progression or death in patients with a best response of CR or PR, assessed per RECIST 1.1 and irRECIST criteria, respectively | Approximately 12 months after dosed | 
| Survival Rate | Survival Rate is defined as the proportion of surviving patients at the corresponding time point. Survival rates at 6 and 12 months will be analyzed in this study | Approximately 12 months after dosed | 
| Incidence of Abnormal Laboratory value | Incidence of abnormal laboratory is defined as the proportion of patients who have abnormal laboratory value not prior to the initiation of MGD013 administration | Approximately 24 months | 
| Incidence of Adverse Events | The incidence of adverse events is defined as the proportion of the patients who have adverse event(s) enrolled in this study. | Approximately 24 months | 
| Incidence of Treatment-Emergent Adverse Events | The incidence of treatment-emergent adverse event is defined as any event not present prior to the initiation of MGD013 treatment or any event already present that worsens in either intensity or frequency following exposure to MGD013 administration. | Approximately 24 months. | 
| Maximum Serum Concentration (Cmax) | The maximum serum concentration (Cmax, ng/ml) is defined as the maximum (or peak) serum concentration that MGD013 achieves in patients after the MGD013 administration at a corresponding timepoint. | Approximately 3 months. | 
| Trough Serum Concentration (Ctrough) | The through serum concentration (Cmin, ng/ml) is defined as the minimum (or through) serum concentration reached by MGD013 prior to administration of a second dose. | Approximately 3 months | 
| Immunogenicity of MGD013 | Immunogenicity is defined as the positivity measured as the anti-MGD013 antibody induced in serum after MGD013 is administrated into human body at corresponding timepoints. | Approximately 6 months after dosed | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, MGD013