This study is a four-cohort, open-label, single-center Phase II clinical trial aimed at evaluating the efficacy and safety of MRG003 alone or in combination with pertuzumab in patients with recurrent or metastatic adenoid cystic carcinoma (ACC) and other salivary gland cancers (non- ACC SGCs). This study is an exploratory one without a randomized control. After fully informed and signing the informed consent form, eligible subjects will be enrolled in MRG003 treatment \[Cohort 1 (ACC) and Cohort 2 (non-ACC SGCs) \] in the order of the study sequence. After the completion of enrollment in Cohort 1, subsequent eligible ACC subjects will be included in the MRG003 plus pertuzumab treatment (Cohort 3), and after the completion of enrollment in Cohort 2, subsequent eligible non-ACC SGC subjects will be included in the MRG003 plus pertuzumab treatment (Cohort 4). Patients in Cohort 1 and Cohort 2 will receive intravenous infusion of MRG003 on the first day of each treatment cycle at a dose of 2.3 mg/kg. Patients in Cohort 3 and Cohort 4 will receive intravenous infusion of pertuzumab on the first day of each treatment cycle at a dose of 3 mg/kg (up to a maximum of 200 mg), followed by MRG003 at a dose of 2.0 mg/kg at least 30 minutes after the completion of pertuzumab infusion. All patients will receive single-agent or combination therapy every three weeks until the end of two years of treatment or the occurrence of a treatment discontinuation event as specified in the protocol. After the treatment, safety follow-up and survival follow-up will be conducted for each subject. For subjects who end treatment due to reasons other than disease progression or death and have not started a new anti-tumor study, tumor imaging assessment will continue as originally planned until disease progression, initiation of new anti-tumor treatment, withdrawal of informed consent, loss to follow-up, or death, whichever occurs first. During the clinical study, we will establish PDX models for mechanism validation. In addition, it is recommended to analyze the following markers for subjects: IHC: ER, PR, AR, HER2, EGFR; FISH: HER2. Genetic testing is recommended based on the economic conditions of the subjects, but it is not mandatory. For subjects with HER2 3+ or HER2 2+ and FISH positive, it is recommended to receive anti-HER2 treatment first. For subjects who have undergone testing, we will collect the test results. For subjects who have not undergone testing, we will conduct relevant tests.
The subject must provide voluntary informed consent and agree to comply with all protocol requirements.
The subject must be at least 18 years of age on the date of informed consent form signing, with no restrictions based on gender.
Expected survival duration of at least 12 weeks.
Histopathologically confirmed recurrent or metastatic salivary gland cancer that cannot be treated with curative surgery or radiotherapy, including major subtypes such as adenoid cystic carcinoma, mucoepidermoid carcinoma, and adenocarcinoma; and immunohistochemically confirmed EGFR expression or positivity.
A history of other malignancies within the past five years is exclusionary, except for adequately treated and cured cervical carcinoma in situ, thyroid cancer (excluding medullary or anaplastic types), or basal cell carcinoma of the skin.
Administration of an antibody-drug conjugate (ADC) with a monomethyl auristatin E (MMAE) payload within 3 months prior to first dose;
Exposure to any investigational agent in a clinical trial within 28 days prior to first dose;
Receipt of systemic anti-tumor therapy (including chemotherapy, radiotherapy, targeted therapy, or other modalities) within 28 days prior to first dose;
Sequential
MRG 003
Druganti EGFR ADC
Pucotenlimab
DrugPD-1 inhibitor
The objective response rate (ORR) was evaluated by investigators using RECIST 1.1 criteria.
The objective response rate (ORR) is defined as the proportion of subjects in whom the tumor has achieved either complete remission (CR) or partial remission (PR) following treatment.
Disease Control Rate (DCR) assessed by the investigator according to RECIST v1.1 criteria
The disease control rate (DCR) is defined as the proportion of subjects in the full analysis set (FAS) whose best overall response is either complete response (CR), partial response (PR), or stable disease (SD) based on investigator assessment using RECIST v1.1. Subjects with SD must have maintained SD for at least 6 weeks from the first dose to be counted as disease control.
Duration of Response
The time from the first documented evidence of objective response (CR or PR) to the first documented disease progression or death from any cause, whichever occurred first.
Progression-Free Survival
The time from the first dose to the first documented disease progression as determined by investigator assessment according to RECIST v1.1, or death from any cause, whichever occurred first.
Overall survival
The time from first dose to death from any cause.
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Ji Dongmei
Lead sponsor
Fudan University
Sponsor institution
