An Open-label, Multi-center, Phase II Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of MRG002 in Patients With HER2-positive/HER2-low Locally Advanced or Metastatic Gastric/ Gastroesophageal Junction Cancer.
Overview
- Phase
- Phase 2
- Intervention
- MRG002
- Conditions
- Locally Advanced Gastric Cancer
- Sponsor
- Shanghai Miracogen Inc.
- Enrollment
- 60
- Locations
- 3
- Primary Endpoint
- Objective Response Rate (ORR)
- Last Updated
- 4 years ago
Overview
Brief Summary
The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG002 as single agent in patients with HER2-positive /HER2-low locally advanced or metastatic gastric/ gastroesophageal junction cancer.
Detailed Description
There are two cohorts in this study. HER2-positive and HER2-low patients will be allocated to cohort 1 and cohort 2, respectively. When the 20th, 40th, or 60th patient in each cohort completed at least one post-baseline tumor assessment, the Safety Monitoring Committee will review the safety and efficacy of these patients to determine dose selection, enrollment continuation, study population, and sample size.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing to sign the ICF and follow the requirements specified in the protocol.
- •Life expectancy ≥ 3 months.
- •Patients with histologically or cytologically confirmed gastric/ gastroesophageal junction cancer.
- •In Cohort 1, a positive HER2 test result defined as follows: IHC 3+ or IHC 2+ and ISH positive. In Cohort 2, low HER2 expression defined as follows: IHC 1+, or IHC 2+ and ISH negative.
- •Documented tumor progression or intolerance during or after at least one prior line of platinum- and/or fluoropyrimidine-based chemotherapy ± anti-HER2 (trastuzumab or equivalent) therapy.
- •Willing and able to provide adequate archival tumor tissue samples for HER2 status confirmation by central laboratory.
- •Cohort 1 patients, who have received prior anti-HER2 therapy, are willing to undergo fresh tissue biopsy to confirm HER2 status as assessed by the investigator to be feasible and safe.
- •Patients must have at least one measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
- •The score of ECOG for performance status is 0 or 1 with no deterioration within 2 weeks prior to the first dose of the study drug.
- •Organ function must meet the basic requirements.
Exclusion Criteria
- •Patients with the following pathological diagnosis: squamous cell carcinoma, carcinoid tumor, neuroendocrine carcinoma, undifferentiated carcinoma, or other unclassifiable gastric cancer.
- •Peripheral neuropathy ≥ Grade 2 per CTCAE 5.
- •Prior treatment with HER2-targeted ADC.
- •Known allergic reaction to any component or excipient of MRG002, or known allergic reaction to trastuzumab or other prior anti-HER2 or other monoclonal antibodies ≥ Grade
- •Presence of untreated or uncontrolled central nervous system (CNS) metastases.
- •Patients received chemotherapy, biological therapy, radical radiotherapy or other anti-tumor treatment within 3 weeks prior to the first dose of the study drug.
- •Any severe cardiac dysfunction, history of myocardial infarction, stroke, or transient ischemic attack (TIA) within 6 months prior to enrollment.
- •Pulmonary embolism or deep venous thrombosis within 3 months prior to the first dose of the study drug.
- •Tumor lesions with bleeding tendency or treated with blood transfusion within 2 weeks prior to the first dose of the study drug.
- •Toxicities due to prior anti-cancer therapy have not resolved to ≤ Grade 1 (CTCAE v5.0).
Arms & Interventions
MRG002
MRG002 will be administrated by an IV infusion of 2.6 mg/kg on Day 1 of every 3 weeks (21-day cycle).
Intervention: MRG002
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: Baseline to study completion, up to 24 months
ORR is defined as the percentage of patients with a complete response (CR) and partial response (PR) according to RECIST v1.1.
Adverse Events (AEs)
Time Frame: Baseline to 45 days after the lase dose of study treatment.
Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug.
Secondary Outcomes
- Progression Free Survival (PFS)(Baseline to study completion, up to 24 months.)
- Overall Survival (OS)(Baseline to study completion, up to 24 months.)
- Duration of Response (DoR)(Baseline to study completion, up to 24 months.)
- Pharmacokinetics (PK) Parameter of MRG002: concentration-time curve(Baseline to 30 days after the last dose of study treatment)
- Immunogenicity (ADA)(Baseline to 30 days after the last dose of study treatment.)
- Disease Control Rate (DCR)(Baseline to study completion, up to 24 months.)