rapid changes in the treatment mode of melanoma worldwide and in China and the development strategy change

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.

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.

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