Clinical trial NCT04868344: A Study of MRG003 in Patients With Advanced Solid Tumors
Official title: An Open-Label, Dose-Finding, Phase I Study in Solid Tumors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: MRG003
Antibody Drug Conjugate (ADC)
Solid tumors
Lead sponsor: Shanghai Miracogen Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-30
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose Limiting Toxicity (DLT) - Phase Ia
timeFrame: First cycle (21 days)
measure: Objective Response Rate (ORR) - Phase Ib
timeFrame: Baseline to study completion (up to 24 weeks)
Secondary outcomes:
measure: PK parameter for MRG003: Maximum Drug Concentration (Cmax)
timeFrame: Baseline to study completion (up to 24 weeks)
measure: PK parameter for MRG003: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast)
timeFrame: Baseline to study completion (up to 24 weeks)
measure: PK parameter for total antibody (TAb): Cmax
timeFrame: Baseline to study completion (up to 24 weeks)
measure: PK parameter for TAb: AUClast
timeFrame: Baseline to study completion (up to 24 weeks)
measure: PK parameter for Monomethyl Auristatin E (MMAE): Cmax
timeFrame: Baseline to study completion (up to 24 weeks)
measure: PK parameter for MMAE: AUClast
timeFrame: Baseline to study completion (up to 24 weeks)
measure: Immunogenicity
timeFrame: Baseline to study completion (up to 24 weeks)
measure: Progression Free Survival (PFS) - Phase Ib only
timeFrame: Baseline to study completion (up to 24 weeks)
measure: Duration of Response (DoR) - Phase Ib only
timeFrame: Baseline to study completion (up to 24 weeks)
measure: Overall Survival (OS) - Phase Ib only
timeFrame: Baseline to study completion (up to 24 weeks)
measure: Incidence of Adverse Events (AEs)
timeFrame: Baseline to 30 days after the last dose of study treatment
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Ruihua Xu, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Qiu MZ, Zhang Y, Guo Y, Guo W, Nian W, Liao W, Xu Z, Zhang W, Zhao HY, Wei X, Xue L, Tang W, Wu Y, Ren G, Wang L, Xi J, Jin Y, Li H, Hu C, Xu RH. Evaluation of Safety of Treatment With Anti-Epidermal Growth Factor Receptor Antibody Drug Conjugate MRG003 in Patients With Advanced Solid Tumors: A Phase 1 Nonrandomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1042-1046. doi: 10.1001/jamaoncol.2022.0503.