Clinical trial NCT04653038: A Study to Evaluate the Safety and Efficacy of MGD013 in Patients With Melanoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Unresectable, Recurrent or Metastatic Melanoma
Untreated Mucosal or Acral Lentiginous Melanoma
Keywords: Melanoma
MGD013
Lead sponsor: Zai Lab (Hong Kong), Ltd.
Sponsor class: INDUSTRY
First posted: 2020-12-04
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Approximately 12 months after dosed
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Approximately 12 months after dosed
measure: Objective Response Rate (ORR)
timeFrame: Approximately 12 months after dosed
measure: Overall Survival (OS)
timeFrame: Approximately 24 months
measure: Progression-free Survival (PFS)
timeFrame: Approximately 12 months after dosed
measure: Disease Control Rate (DCR)
timeFrame: Approximately 12 months after dosed
measure: Duration of Response (DoR)
timeFrame: Approximately 12 months after dosed
measure: Survival Rate
timeFrame: Approximately 12 months after dosed
measure: Incidence of Abnormal Laboratory value
timeFrame: Approximately 24 months
measure: Incidence of Adverse Events
timeFrame: Approximately 24 months
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Approximately 24 months.
measure: Maximum Serum Concentration (Cmax)
timeFrame: Approximately 3 months.
measure: Trough Serum Concentration (Ctrough)
timeFrame: Approximately 3 months
measure: Immunogenicity of MGD013
timeFrame: Approximately 6 months after dosed
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Chang chun
country: China
facility: The first hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Xi'an
country: China
facility: Tangdu Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Shaw Hospital, School Of Medicine ,Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun GUO
role: PRINCIPAL_INVESTIGATOR
References: