Clinical trial NCT05135715: A Study of RC48-ADC in Advanced Melanoma Subjects With HER2 Variant (Mutation, Amplification, Overexpression)
Official title: A Single-arm, Multicentre, Open Phase Ⅱa Clinical Study of RC48-ADC in the Treatment of HER2 Variant (Mutation, Amplification, Overexpression) Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Melanoma, Stage II
HER2-positive
Advanced Melanoma
Keywords: RC48-ADC
HER2-positive melanoma
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-11-26
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

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.

Primary outcomes:
measure: Objective remission rate (ORR)
timeFrame: within approximately 3 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: within approximately 3 years
measure: Duration of relief (DOR)
timeFrame: within approximately 3 years
measure: Disease control rate (DCR)
timeFrame: within approximately 3 years
measure: Overall survival (OS)
timeFrame: within approximately 3 years
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian cancer hospital
state: Fujian
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Hangzhou
country: China
facility: Zhejiang cancer hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Cancer Hospital
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Guo, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: