An Open-Label, Multi-Center Phase II Clinical Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent Metastatic Nasopharyngeal Carcinoma

Shanghai Miracogen Inc.23 sites in 1 country238 target enrollmentApril 6, 2023

ConditionsRecurrent or Metastatic Nasopharyngeal Carcinoma

InterventionsMRG003 Capecitabine tablets Docetaxel injection

DrugsMRG003 Capecitabine tablets Docetaxel injection

Overview

Phase: Phase 2
Intervention: MRG003
Conditions: Recurrent or Metastatic Nasopharyngeal Carcinoma
Sponsor: Shanghai Miracogen Inc.
Enrollment: 238
Locations: 23
Primary Endpoint: Objective Response Rate (ORR) by Independent Review Committee (IRC)
Status: Active, not recruiting
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG003 in patients with recurrent metastatic nasopharyngeal carcinoma.

Detailed Description

The study consists of two stages. Part A of this study is an open-label, single arm, multicenter Phase IIa clinical study in patients with inoperable, radiotherapy ineligible RM-NPC who have failed (or are intolerable) at least 1 prior line platinum-based systemic chemotherapy and PD-1 (L1) inhibitors. Part B is an open-label, randomized, multicenter Phase IIb study to compare the efficacy and safety of MRG003 versus capecitabine/docetaxel in patients with RM-NPC who have failed at least 2 prior lines of systemic chemotherapy and PD-1 (L1) inhibitors.

Registry

clinicaltrials.gov

Start Date

April 6, 2023

End Date

December 30, 2026

Last Updated

2 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Shanghai Miracogen Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Willing to sign the ICF and follow the requirements specified in the protocol.
•Age: ≥18 years, ≤75 years
•Expected survival time\>3 months.
•Patients with histologically confirmed unresectable, radiation-ineligible recurrent metastatic nasopharyngeal carcinoma.
•Part A: Metastatic nasopharyngeal carcinoma that has failed or recurred or was intolerant to at least 1 prior line platinum-based systemic chemotherapy and PD-1/PD-L1 inhibitors
•Part B: have documented failure of at least 2 prior lines of PD-1 (L1) and therapysystemic chemotherapy, which include at least platinum-based regimen, gemcitabine, taxanes/capecitabine.
•Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
•ECOG performance score 0 or
•Organ functions and coagulation function must meet the basic requirements.
•No severe cardiac dysfunction with left ventricular ejection fraction (LVEF) ≥ 50%.

Exclusion Criteria

•Grade ≥2 peripheral neuropathy per CTCAE v5.
•Is expected to require surgery or any other form of systemic or local anti-tumor therapy during the study.
•Received systemic chemotherapy, targeted therapy, biologics or immunotherapy, or major surgery (except for minor surgery within 2 weeks and fully recovered) within 3 weeks prior to the first dose of study treatment; received thoracic radiotherapy \>30 Gy within 6 months prior to the first dose of study treatment; received prior radiotherapy (except radiotherapy for CNS, wash-out period ≥ 28 days is required) within 14 days before the first dose of study treatment, received traditional Chinese medicine with anti-tumor indications within the 2 weeks before the first dose of study treatment.
•Known active central nervous system (CNS) metastases and/or meningeal metastases. Patients with brain metastases may participate provided they are treated and stable
•Residual toxicities due to prior anti-tumor therapy (including biologics, targeted therapy, immunotherapy, chemotherapy or radiotherapy) or ≥ Grade 1 (CTCAE v5.0) clinically significant laboratory abnormality.
•History of severe cardiac dysfunction, stroke, or transient ischemic attack (TIA) within 6 months prior to enrollment. History of ventricular tachycardia or torsades de pointes. Any clinically important abnormality in the rhythm, conduction, or morphology of the resting ECG. Note: Patients with arrhythmia are eligible if they are receiving antiarrhythmic medication and the screening electrocardiogram (ECG) shows controllable rhythm and heart rate.
•Pulmonary embolism or deep venous thrombosis within 3 months prior to the first dose of study drug.
•Known history of malignancy (except for patients with cutaneous basal cell carcinoma, superficial bladder carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in situ, or papillary thyroid carcinoma who have undergone successful curative treatment) unless the patient has received potentially curative therapy and has not had disease recurrence within 5 years starting from the treatment.
•Note: The 5-year recurrence-free time requirement does not apply to NPC for which the patient is enrolled.
•Uncontrolled or poorly controlled hypertension (e.g., systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg) or diabetes mellitus (glycosylated hemoglobin (HbA1c) \> 8%).

Arms & Interventions

MRG003

Part A: On the first day of every 3 weeks, MRG003 will be administered via intravenous infusion at 2.0 mg/kg or 2.3 mg/kg calculated based on the actual body weight. Part B: On the first day of every 3 weeks, MRG003 will be administered via intravenous infusion at 2.3 mg/kg calculated based on the actual body weight.

Intervention: MRG003

Capecitabine tablets/Docetaxel injection

Part B: Capecitabine tablets: 1000 mg/m2, bid, d1-14, po, Q3W, or Docetaxel injection: 75 mg/m2, d1, IV, Q3W

Intervention: Capecitabine tablets

Capecitabine tablets/Docetaxel injection

Part B: Capecitabine tablets: 1000 mg/m2, bid, d1-14, po, Q3W, or Docetaxel injection: 75 mg/m2, d1, IV, Q3W

Intervention: Docetaxel injection

Outcomes

Primary Outcomes

Objective Response Rate (ORR) by Independent Review Committee (IRC)

Time Frame: Baseline to disease progression, intolerable drug-related toxicities, withdrawal of consent, or study discontinuation for any reasons (up to 24 months)

ORR is defined as the proportions of patients with a complete response (CR) and partial response (PR). ORR will be assessed by Independent Review Committee (IRC) according to RECIST v1.1.

Secondary Outcomes

Disease Control Rate (DCR)(Baseline to Baseline to disease progression, intolerable drug-related toxicities, withdrawal of consent, or study discontinuation for any reasons (up to 24 months))
PK parameter for TAb: AUClast(Baseline to 30 days after the last dose of study treatment.)
Objective Response Rate (ORR) by Investigator(Baseline to Baseline to disease progression, intolerable drug-related toxicities, withdrawal of consent, or study discontinuation for any reasons (up to 24 months))
PK parameter for MRG003: (AUClast)(Baseline to 30 days after the last dose of study treatment.)
Duration of Response (DoR)(Baseline to Baseline to disease progression, intolerable drug-related toxicities, withdrawal of consent, or study discontinuation for any reasons (up to 24 months))
Adverse Events (AEs)(Baseline to 30 (for AE) and 45 (for SAE) days after the last dose of study treatment.)
PK parameter for MRG003: (Cmax)(Baseline to 30 days after the last dose of study treatment)
PK parameter for total antibody (TAb): Cmax(Baseline to 30 days after the last dose of study treatment.)
Progression Free Survival (PFS)(Baseline to Baseline to disease progression, intolerable drug-related toxicities, withdrawal of consent, or study discontinuation for any reasons (up to 24 months))
Overall Survival (OS)(Sign the informed consent form to Baseline to disease progression, intolerable drug-related toxicities, withdrawal of consent, or study discontinuation for any reasons (up to 24 months))
PK parameter for MMAE: AUClast(Baseline to 30 days after the last dose of study treatment.)
The proportion of patients with positive ADA immunogenicity results.(Baseline to 30 days after the last dose of study treatment.)
PK parameter for Monomethyl Auristatin E (MMAE): Cmax(Baseline to 30 days after the last dose of study treatment.)