A Study to Evaluate the Efficacy and Safety of IBI363 Monotherapy Compared to Pembrolizumab in Patients With Unresectable Locally Advanced or Metastatic Mucosal or Acral Melanoma Who Had Not Previously Received Systemic Therapy

A Phase II, Open-label, Randomized, Multi-center Study to Evaluate the Efficacy and Safety of IBI363 Monotherapy Compared to Pembrolizumab in Patients With Unresectable Locally Advanced or Metastatic Mucosal and Acral Melanoma Who Had Not Previously Received Systemic Therapy

This is a Phase II, open-label, randomized, multi-center study to assess the efficacy and safety of IBI363 monotherapy compared to Pembrolizumab in the treatment of patients with unresectable locally advanced or metastatic mucosal or acral melanoma who had not previously received systemic therapy.

Inclusion Criteria:

1. Histologically or cytologically confirmed unresectable, locally advanced or metastatic mucosal or acral-type melanoma, according to the American Joint Committee on Cancer (AJCC) 8th edition stage III-IV.

2. No prior systemic treatment for unresectable or metastatic melanoma; Prior adjuvant or neoadjuvant therapy (except for disease progression to unresectable or metastatic melanoma during adjuvant or neoadjuvant therapy or within 6 months after treatment discontinuation) was permitted.

3. Have at least one measurable lesion (target lesion) according to RECIST v1.1. For lesions that have previously received radiotherapy or intratumoral injection, measurable lesions that progress to the criteria specified in RECIST1.1 after treatment may be considered.

   The target lesions of this study must be measured by imaging (enhanced CT or MRI. Plain scan CT or MRI can be accepted after communication with the sponsor if the subjects are allergic to contrast media or have other conditions that are not suitable for enhanced CT or MRI).

   Skin lesions or other superficial sites that cannot be repeatedly measured by imaging can only be used as non-target lesions.

4. The Eastern Cooperative Oncology Group Physical Status Score (ECOG PS) is 0 or 1.

5. Expected survival time no less than 3 months.

6. Female subjects of childbearing age or male subjects whose partner is a female of childbearing age agree to strictly use effective contraception throughout the treatment period and for 6 months after the treatment period.

7. Breastfeeding women must agree to strictly refrain from breastfeeding during the entire treatment period and for 6 months after the treatment period.

Exclusion Criteria:

1. Women who are pregnant or plan to become pregnant within 6 months before, during, or after the last dose of the study drug.

2. Active or symptomatic central nervous system metastases

3. Any of the following hematological abnormalities were present at baseline * (within 7 days before the first administration of the study drug) :

   Hemoglobin <90 g/L The absolute count of neutrophils (ANC) was <1.5×10^9/L Platelet count <100×10^9/L

4. Any of the following serum biochemical abnormalities are present at baseline (within 7 days before the first dose) :

   Total bilirubin >1.5× Upper limit of normal (ULN); Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >3×ULN; For liver metastasis, AST or ALT > 5.0×ULN; With serum Creatinine >1.5×ULN or Clearance of Creatinine (CCr) <45 mL/min, CCr (using actual body weight) was calculated using Cockcroft-Gault formula (Appendix 3).

   Albumin <30 g/L.

5. Any of the following coagulation parameters are abnormal at baseline (within 7 days before the first dose) :

   International normalizaed ratio (INR) >1.5×ULN (>3×ULN if receiving steady dose anticoagulant therapy); Partial thromboplastin time (PTT) (or activated partial thromboplastin time, [activated partial thromboplastin time, PTT) aPTT]) >1.5×ULN (>3×ULN if receiving steady dose anticoagulant therapy).

6. There is a history of active thrombosis or deep vein thrombosis or pulmonary embolism in the 4 weeks prior to initial administration of the investigatory drug, unless the disease is adequately treated and is considered stable by the investigator.

7. Uncontrolled bleeding or a known tendency to bleed.

8. Cardiovascular and cerebrovascular diseases of significant clinical significance.

9. History of interstitial pneumonia, pulmonary fibrosis, pneumoconiosis, drug-related pneumonia, radiation pneumonia, etc. requiring steroid hormone or other treatment, as well as severe abnormal lung function or other forms of restrictive lung disease.

10. An active autoimmune disease requiring systemic treatment (e.g. with disease-modifying drugs, corticosteroids, or immunosuppressants) has occurred within 2 years prior to first administration. Replacement therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic.