An Open-Label, Multi-center, Phase I/II Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Anti-Tumor Activity and Pharmacokinetics of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- MRG004A
- Conditions
- Advanced or Metastatic Solid Tumors
- Sponsor
- Shanghai Miracogen Inc.
- Enrollment
- 181
- Locations
- 9
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The objective of this study is to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of MRG004A in patients with Tissue Factor positive advanced or metastatic solid tumors.
Detailed Description
This study consists of two parts. Part A is a dose escalation study to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of MRG004A. Part B is a disease specific multi-cohort dose expansion study to further assess the efficacy and safety of MRG004A at confirmed RP2D.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Understands and provides written informed consent and willing to follow the requirements specified in protocol.
- •Age ≥18 years.
- •Life expectancy ≥6 months.
- •For Part B patients, documented Tissue Factor (TF) presence in tumor biopsy specimens obtained from archival or re-biopsy specimens by immunohistochemistry (IHC) protein expression.
- •Must have histologically or cytologically confirmed unresectable or metastatic cancer with documented disease progression during prior therapy, or relapse or progression following approved standard therapy for their tumor types- Part A and Part B.
- •Part B: Patients who have documented progression during or relapse following standard therapy, no further treatment options that are known to improve survival, and participation in a clinical trial is a reasonable therapeutic option.
- •Patients must have measurable disease per RECIST v1.
- •ECOG performance status of 0 or
- •Acceptable bone marrow, hepatic, cardiac, renal, and coagulation function.
- •A negative serum pregnancy test if female and aged between 18-55 years old.
Exclusion Criteria
- •Archival or biopsy tumor shows TF IHC membrane or cytosolic score of zero, no TF-positive expression or no TF-positive staining in Part B patients.
- •Toxicities (except alopecia \& fatigue) due to prior antitumor therapy are greater than CTCAE v5.0 Grade
- •Toxicities due to prior radiotherapy that have not resolved to Grade ≤ 1 CTCAE v5.0 at least 21 days prior to the first treatment.
- •Untreated, unstable or uncontrolled central nervous system (CNS) metastases.
- •Any other type of anti-cancer therapy within 21 days of the first dose of study treatment. Use of any other type of anti-cancer treatment is prohibited throughout the study.
- •Patients with increased bleeding risk.
- •Presence of severe cardiac dysfunction.
- •Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug.
- •Concurrent malignancy within 5 years prior to entry.
- •Uncontrolled or poorly controlled hypertension.
Arms & Interventions
MRG004A
All patients in Part A (dose escalation) and Part B (dose expansion) will be administrated MRG004A on Day 1 of every 3 weeks (21-day cycle).
Intervention: MRG004A
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: Baseline to study completion (up to 24 months)
The proportion of patients who achieve complete response (CR) or partial response (PR) as assessed by the Independent Central Review (ICR).
Maximum Tolerated Dose (MTD)
Time Frame: DLT will be evaluated during the first treatment cycle (Day 1-21)
The highest dose confirmed wherein less than 2 out of 6, or \< 33% of evaluable patients in a treatment cohort experiences dose-limiting toxicity (DLT).
Recommended Phase II Dose (RP2D)
Time Frame: Baseline to study completion (up to 24 months)
The dose level of MRG004A recommended for further clinical studies based on assessment of the safety, efficacy and PK data from Part A of this study.
Adverse Events (AEs)
Time Frame: From signing informed consent until 45 days after the last dose of MRG004A
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
- Disease Control Rate (DCR)(Baseline to study completion (up to 24 months))
- Pharmacokinetics (PK) Parameter of MRG004A: Tmax(Baseline to 30 days after the last dose of study treatment)
- Incidence of anti-drug antibody (ADA)(Baseline to 30 days after the last dose of study treatment)
- Progression Free Survival (PFS)(Baseline to study completion (up to 24 months))
- Duration of Response (DoR)(Baseline to study completion (up to 24 months))
- Pharmacokinetics (PK) Parameter of MRG004A: Cmax(Baseline to 30 days after the last dose of study treatment)
- Overall Survive (OS)(Baseline to study completion (up to 24 months))
- Pharmacokinetics (PK) Parameter of MRG004A: AUClast(Baseline to 30 days after the last dose of study treatment)