A Study of MRG002 in the Treatment of Patients With HER2-expressed Advanced Malignant Solid Tumors.

Sponsor

Shanghai Miracogen Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05338957

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this study is to assess the safety and tolerability of MRG002 in combination with HX008 in patients with HER2-expressed advanced malignant solid tumors; and to , explore the maximum tolerated dose (MTD), and to determine the recommended phase II dose (RP2D) of combination therapy; , and to evaluate the preliminary efficacy, pharmacokinetics, and immunogenicity of combination therapy in the targeted study population.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignant Solid Tumors	Drug: MRG002+HX008	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label, Multi-center, Phase I/II Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of MRG002 in Combination With HX008 in Patients With HER2-expressed Advanced Malignant Solid Tumors.

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MRG002+HX008 MRG002 will be administrated via intravenous infusion at 1.8，,2.2, or 2.6 mg/kg , (if appropriate) once on Day 1 of every 3 weeks (21-day cycle), up to 24 months. HX008 will be administrated via intravenous infusion at 3 mg/kg once on Day 1 of every 3 weeks (21-day- cycle), up to 24 months.	Drug: MRG002+HX008 Administrated intravenously

Arm

Intervention/Treatment

Experimental: MRG002+HX008

MRG002 will be administrated via intravenous infusion at 1.8，,2.2, or 2.6 mg/kg , (if appropriate) once on Day 1 of every 3 weeks (21-day cycle), up to 24 months. HX008 will be administrated via intravenous infusion at 3 mg/kg once on Day 1 of every 3 weeks (21-day- cycle), up to 24 months.

Drug: MRG002+HX008

Administrated intravenously

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicity (DLT) in each dose group [Within 28 days after the first dose.]
DLT is defined as any of the treatment emergent adverse events (TEAE) as specified in the protocol that bear a definite, probable, or possible causal relationship to study drug administration within 28 days after the first dose.
Adverse events [After signing informed consent until 90 days after the last dose.]
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.
Recommended Phase II Dose (RP2D) [Baseline to study completion (up to 24 months)]
The dose level of MRG002 recommended for further clinical studies based on assessment of the safety, efficacy and PK data from this study.

Secondary Outcome Measures

Objective Response Rate (ORR) [Baseline to study completion (up to 24 months)]
ORR is defined as the proportion of subjects with CR and PR according to RECIST v1.1.
Duration of Response (DOR) [Baseline to study completion (up to 24 months)]
DOR is defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause.
Disease Control Rate (DCR) [Baseline to study completion (up to 24 months)]
DCR is defined as the proportion of subjects achieving CR, PR, and SD after treatment.
Progression Free Survival (PFS) [Baseline to study completion (up to 24 months)]
PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause.
Time to Response (TTR) [Baseline to study completion (up to 24 months)]
TTR is defined as the time from the start of treatment until the first occurrence of CR or PR by tumor assessment.
Overall Survival (OS) [Baseline to study completion (up to 24 months)]
OS is defined as the duration from the start of treatment to death of any cause.
PK parameters: concentration-time curve [Baseline to 90 days after the last dose.]
Plot of drug concentration changing with time after drug administration.
Immunogenicity (ADA) [Baseline to 90 days after the last dose.]
The proportion of patients with positive ADA results.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Willing to sign the informed consent form and follow the requirements specified in the protocol.
Aged 18 to 75 (including 18 and 75), both genders.
Life expectancy ≥ 12 weeks.
Patients with histopathological or cytological confirmed HER2-expressed advanced solid tumors, and with at least one measurable lesion according to the Response Criteria in Solid Tumors (RECIST v1.1).
The score of ECOG for performance status is 0 or 1.
The toxicity of previous anti-tumor treatment has recovered to ≤ Grade 1 as defined by NCI-CTCAEv5.0.
No severe cardiac dysfunction.
Organ functions must meet the basic requirements.
Cumulative dose of anthracycline ≤ 450 mg/m2 doxorubicin or its equivalent.

Exclusion Criteria:

Prior treatment with chemotherapy, biological therapy, immunotherapy, radiotherapy, investigational drugs, attenuated live vaccines, immunomodulators, CYP3A4 inhibitors/inducers, antibody-drug conjugates, etc.
Treatment with immune checkpoint inhibitors or tumor vaccines within 60 days prior to the first dose.
Treatment with systemic corticosteroids or other immunosuppressive drugs within 14 days prior to the first dose or during the study period.
History of severe cardiac disease.
Poorly controlled hypertension and hyperglycemia.
Presence of peripheral neuropathy ≥ Grade 2.
History of moderate or severe dyspnea at rest due to advanced malignant tumor or its complications or severe primary pulmonary disease, or current need of continuous oxygen therapy, or current interstitial lung disease or pneumonia.
Central nervous system metastasis.
Received major surgery within 4 weeks prior to the first dose without complete recovery.
History of hypersensitivity to any component of MRG002 or HX008 or known history of hypersensitivity of ≥ Grade 3 to macromolecular protein products/monoclonal antibodies.
Evidence of active infection.
History of primary immunodeficiency or autoimmune disease.
Female patients with a positive serum pregnancy test or who are breast-feeding or who do not agree to take adequate contraceptive measures during the treatment and for 6 months after the last dose of study treatment.
Previous history of other primary malignancies.
Other conditions inappropriate for participation in this study, as deemed by the investigator.