A Study of RC48-ADC in Advanced Melanoma Subjects With HER2 Variant (Mutation, Amplification, Overexpression)

A Single-arm, Multicentre, Open Phase Ⅱa Clinical Study of RC48-ADC in the Treatment of HER2 Variant (Mutation, Amplification, Overexpression) Advanced Melanoma

This is a Phase IIa, single-arm, multicentre, open-label clinical trial aims to evaluate the effectiveness and safety of RC48-ADC in the treatment of HER2 Variant (Mutation, Amplification, Overexpression) advanced melanoma.

Study Overview

• Status: Recruiting
• Conditions: Advanced Melanoma; Melanoma, Stage II; HER2-positive
• Intervention / Treatment: Drug: RC48-ADC

Detailed Description

This study is a phase IIa multicentre,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 mutation is defined as the presence of HER2 gene mutations in primary or metastatic tumour tissue as detected by immunohistochemistry (IHC). HER2 gene mutation.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianming Fang, Ph.D; Phone Number: +8610-58075763; Email: jianminfang@hotmail.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital
    • Contact: Jun Guo
  • Fujian
    • Fuzhou, Fujian, China
      • Recruiting
      • Fujian cancer hospital
  • Jilin
    • Changchun, Jilin, China
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: Ti Wu, M.D
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Meiyu Fang, M.D

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC48-ADC; 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; 2.0 mg/kg IV every 2 weeks; 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
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
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
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

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.
• Investigators: Principal Investigator: Jun Guo, Ph.D, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: November 15, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 18, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: RC48-ADC; HER2-positive melanoma
• 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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: RC48-C020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No