A Study of RC48-ADC in Advanced Melanoma Subjects With HER2-positive

Study Overview
=================
Brief Summary
-----------------
This is a Phase IIa, single-arm, single-center, open-label clinical trial aims to evaluate the effectiveness and safety of RC48-ADC in the treatment of HER2-positive advanced melanoma.

Detailed Description
-----------------
This study is a phase IIa single-center, single-arm, open-label, clinical study to evaluate the efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody-Monomethyl auristatin E (MMAE) conjugate for the treatment of HER2- positive advanced melanoma. HER2 positive is defined as the expression of HER2 protein in the primary tumor or metastatic tumor tissue as IHC 2+ or IHC 3+ by immunohistochemistry (IHC).

Official Title
-----------------
A Single-arm, Single-center, Open Phase Ⅱa Clinical Study of RC48-ADC in the Treatment of HER2-positive Advanced Melanoma

Conditions
-----------------
Melanoma, Stage II, HER2-positive, Advanced Melanoma

Intervention / Treatment
-----------------
* Drug: RC48-ADC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Voluntary agreement to provide written informed consent. Male or female, Age ≥ 18 years. Predicted survival ≥ 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. All female subjects will be considered to be of child-bearing potential unless participants are postmenopausal, or have been sterilized surgically.Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol. Adequate organ function. All subjects must be histologically confirmed, non-resectable stage III or metastatic melanoma, except for patients with uveal or ocular melanoma. The subject has experienced disease progression or intolerance after receiving standard treatment in the past; Patients with disease progression within 6 months after receiving neoadjuvant or adjuvant chemotherapy regimens can be included in the clinical study. The HER2 IHC test result is IHC 2+ or IHC 3+, the subject's previous test results (confirmed by the investigator) or the research center's test results are acceptable; the subject can provide the Specimen of primary or metastatic tumor for HER2 review/judgment. According to the RECIST 1.1 standard, there is at least one measurable lesion. Exclusion Criteria: Known hypersensitivity to Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection. History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to trial treatment. Pleural or abdominal effusion with clinical symptoms that requires ongoing treatment. Treated with systemic treatment (e.g. immunomodulators, corticosteroids or immunosuppressants) for the autoimmune disease within 2 years prior to the study treatment. History of major surgery within 4 weeks of planned start of trial treatment. Has received a live virus vaccine within 4 weeks of planned start of trial treatment. Toxicity of previous anti-tumor treatment not recovered to CTCAE Grade 0-1 (with exception of Grade 2 alopecia). Pregnancy or lactation. Currently known active infection with HIV or tuberculosis. Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RC48-ADC<br>Participants will receive RC48-ADC every 2 weeks (Q2W) until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first). | Drug: RC48-ADC<br>* 2.0 mg/kg IV every 2 weeks<br>* Other names: Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective remission rate (ORR) | The objective response rate will be analyzed according to the RECIST 1.1 standard tumor evaluation. | within approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard. | within approximately 3 years | 
| Duration of relief (DOR) | DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death. | within approximately 3 years | 
| Disease control rate (DCR) | Disease control rate (DCR) is defined as cases where objective remission (assessed as complete remission or partial remission according to RECIST 1.1 standard) or stable disease during the study. | within approximately 3 years | 
| Overall survival (OS) | Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject. | within approximately 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RC48-ADC, HER2-positive melanoma