A Study of MRG003 in Patients With Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

An Open-Label, Dose-Finding, Phase I Study in Solid Tumors.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04868344
• Other study ID #: MRG003-001
• Status: Completed
• Phase: Phase 1
• Start date: May 9, 2018
• Est. completion date: March 29, 2021

Study information

• Verified date: April 2021
• Source: Shanghai Miracogen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to assess the safety, efficacy, and pharmacokinetics of MRG003, as well as immunogenicity as defined by the incidence of anti-drug antibody (ADA) of MRG003 in patients with advanced solid tumors, including colorectal cancer, squamous cell carcinoma of head and neck, and nasopharyngeal carcinoma.

Description:

This study consists of two parts: Phase Ia dose escalation and Phase Ib dose expansion. The objective of Phase Ia is to determine MTD or RP2D, and Phase Ib is conducted to evaluate efficacy of MRG003 in patients with advanced colorectal cancer, squamous cell carcinoma of head and neck (SCCHN), and nasopharyngeal carcinoma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: March 29, 2021
• Est. primary completion date: March 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Willing to sign the ICF and follow the requirements specified in the protocol.

• Age: =18 years and =75 years, both genders

• Expected survival time=12 weeks

• Phase Ia: Patients with histologically and cytologically confirmed advanced or metastatic solid tumor

• Phase Ib: Patients with histologically and cytologically confirmed EGFR-positive advanced or metastatic colorectal cancer, squamous cell carcinoma of head and neck, and nasopharyngeal carcinoma

• Subjects must have measurable lesions according to the response Evaluation Criteria In Solid Tumors(RECIST v1.1)

• ECOG performance score 0 or 1

• Acceptable liver, renal, and hematologic function

• Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment

Exclusion Criteria:

• History of hypersensitivity to any component of the investigational product

• Presence of central nervous system metastasis

• Prior history of other primary malignancies

• Known history of clinically significant hepatic diseases

• Evidence of active infection of human immunodeficiency virus (HIV)

• History of ophthalmic abnormalities

• Any severe or uncontrolled systemic disease judged by the investigator

• Patients with poorly controlled heart diseases

• Received radiotherapy, chemotherapy, biotherapy, immunotherapy or other anti-tumor drugs within 4 weeks prior to the first dose of study treatment

• Major surgery or surgical therapy for any cause within 4 weeks prior to the first dose of investigational drug

• Planned surgery or surgery is the best interest of patients as determined by investigator

• History of severe skin disease requiring interruption of previous EGFR targeted therapy; or chronic skin disease requiring oral or intravenous therapy

• Active concomitant diseases that might increase risks of toxicity

• Pregnancy, or breast feeding

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• MRG003
Administered intravenously

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Miracogen Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity (DLT) - Phase Ia	DLT is assessed on Day 21 (Day 1 to 21) of the first dose administration.	First cycle (21 days)
Primary	Objective Response Rate (ORR) - Phase Ib	ORR was defined as the proportions of subjects with a complete response (CR) and partial response (PR). ORR will be assessed by investigator according to RECIST v1.1.	Baseline to study completion (up to 24 weeks)
Secondary	PK parameter for MRG003: Maximum Drug Concentration (Cmax)	Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.	Baseline to study completion (up to 24 weeks)
Secondary	PK parameter for MRG003: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)	AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statics.	Baseline to study completion (up to 24 weeks)
Secondary	PK parameter for total antibody (TAb): Cmax	Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.	Baseline to study completion (up to 24 weeks)
Secondary	PK parameter for TAb: AUClast	AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statics.	Baseline to study completion (up to 24 weeks)
Secondary	PK parameter for Monomethyl Auristatin E (MMAE): Cmax	Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics.	Baseline to study completion (up to 24 weeks)
Secondary	PK parameter for MMAE: AUClast	AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statics.	Baseline to study completion (up to 24 weeks)
Secondary	Immunogenicity	Blood samples for anti-drug antibody (ADA) analysis will be collected each time according to the pre-defined timepoints.	Baseline to study completion (up to 24 weeks)
Secondary	Progression Free Survival (PFS) - Phase Ib only	PFS was defined as the duration from the start of treatment to the onset of tumor progression or death of any cause.	Baseline to study completion (up to 24 weeks)
Secondary	Duration of Response (DoR) - Phase Ib only	DOR was defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause.	Baseline to study completion (up to 24 weeks)
Secondary	Overall Survival (OS) - Phase Ib only	OS was defined as the duration from the start of treatment to death of any cause.	Baseline to study completion (up to 24 weeks)
Secondary	Incidence of Adverse Events (AEs)	Incidence of AEs and serious adverse events (SAEs) will be assessed based on NCI-CTCAE v5.0	Baseline to 30 days after the last dose of study treatment