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

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

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.

Study Overview

• Status: Terminated
• Conditions: Unresectable, Recurrent or Metastatic Melanoma; Untreated Mucosal or Acral Lentiginous Melanoma
• Intervention / Treatment: Drug: MGD013

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China
      • Nanjing Drum Tower Hospital
  • Jilin
    • Chang chun, Jilin, China
      • The First Hospital of Jilin University
    • Changchun, Jilin, China
      • Jilin Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center
  • Shanxi
    • Xi'an, Shanxi, China
      • Tangdu Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • Sir Run Shaw Hospital, School Of Medicine ,Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zai Lab (Shanghai) Co., Ltd.
• Investigators: Principal Investigator: Jun Guo, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2020
• Primary Completion (Actual): March 2, 2022
• Study Completion (Actual): March 2, 2022

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 26, 2020
• First Posted (Actual): December 4, 2020

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Melanoma; MGD013
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: ZL-1301-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes