The Safety and Efficacy of MRG003 With or Without Putrelimab in Recurrent or Metastatic Salivary Gland Cancer: a Single-center, Open-label Cohort Study
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Ji Dongmei
- Enrollment
- 68
- Primary Endpoint
- The objective response rate (ORR) was evaluated by investigators using RECIST 1.1 criteria.
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •Histopathological confirmation of recurrent or metastatic salivary gland carcinoma, including major histological subtypes such as adenoid cystic carcinoma, mucoepidermoid carcinoma, and adenocarcinoma, is required.
- •Prior receipt of at least one systemic anti-tumor therapy (e.g., chemotherapy, targeted therapy, or immunotherapy) is required, with documented disease progression or recurrence during or following the most recent treatment.
- •The subject must be able to provide a tumor tissue specimen-either from the primary or metastatic site-for pathological evaluation. Acceptable specimens include formalin-fixed paraffin-embedded blocks, paraffin-embedded sections, or fresh tissue sections. If archived tissue is unavailable, a new biopsy must be performed.
- •According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the subject must have at least one measurable lesion at baseline, defined as a lesion with a longest diameter ≥10 mm on CT imaging (or a short axis ≥15 mm for lymph nodes). Lesions previously irradiated may be considered target lesions if there is radiological evidence of progression; however, non-irradiated lesions are preferred.
- •The Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 within 7 days prior to the first administration of study drug.
- •Organ function must meet the following criteria within 7 days prior to dosing:
- •Hematologic function: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, and hemoglobin ≥90 g/L. Subjects must not have received blood or platelet transfusions within 14 days prior to first dosing, nor growth factor support (e.g., granulocyte colony-stimulating factor or erythropoiesis-stimulating agents) within 7 days prior to first dosing.
Exclusion Criteria
- •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.
- •Prior receipt of any of the following treatments:
- •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;
- •Undergone major surgery within 28 days prior to first dose without full recovery, or scheduled to undergo major surgery during the first 12 weeks following initiation of study treatment.
- •Baseline HER2-positive status without prior HER2-directed therapy.
- •Presence of symptomatic central nervous system (CNS) metastases or leptomeningeal disease; or history of CNS metastasis treatment within 3 months prior to first dose.
- •Clinically significant pleural, peritoneal, or pericardial effusion requiring therapeutic drainage.
- •Any severe or uncontrolled systemic illness, as determined by the investigator, including but not limited to poorly controlled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg), inadequately controlled diabetes mellitus, or evidence of active bleeding.
Arms & Interventions
MRG003 Monotherapy
MRG003 is administered intravenously at 2.3 mg/kg on day 1 of each cycle, every three weeks, as monotherapy, for up to two years or until treatment discontinuation criteria are met.
Intervention: MRG 003 (Drug)
MRG003 combined with Pucontenlimab
MRG003 2.0 mg/kg combined with Pucontenlimab 3.0mg/kg ( ≤ 200mg) on day 1 of each cycle, every three weeks, for up to two years or until treatment discontinuation criteria are met.
Intervention: MRG 003 (Drug)
MRG003 combined with Pucontenlimab
MRG003 2.0 mg/kg combined with Pucontenlimab 3.0mg/kg ( ≤ 200mg) on day 1 of each cycle, every three weeks, for up to two years or until treatment discontinuation criteria are met.
Intervention: Pucotenlimab (Drug)
Outcomes
Primary Outcomes
The objective response rate (ORR) was evaluated by investigators using RECIST 1.1 criteria.
Time Frame: From the date of the first dose of Cycle 1 (each cycle is 21 days) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
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.
Secondary Outcomes
- Disease Control Rate (DCR) assessed by the investigator according to RECIST v1.1 criteria(From the date of the first dose of Cycle 1 (each cycle is 21 days) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.)
- Duration of Response(From the date of the first objective response (according to Recist 1.1) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.)
- Progression-Free Survival(From the date of the first dose of Cycle 1 (each cycle is 21 days) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.)
- Overall survival(From the date of the first dose of Cycle 1 (each cycle is 21 days) until the date of death from any cause, assessed up to 60 months.)
- Safety Assessments(From the date of the first dose of Cycle 1 (each cycle is 21 days) until the date 30 days after last dose or the date of death, whichever occurs first, assessed up to 60 months.)
- Dose Modification and Discontinuation Rates(From the date of the first dose of Cycle 1 (each cycle is 21 days) until the date 30 days after last dose or the date of death, whichever occurs first, assessed up to 60 months.)
Investigators
Ji Dongmei
professor
Fudan University