Clinical trial NCT05338957: A Study of MRG002 in the Treatment of Patients With HER2-expressed Advanced Malignant Solid Tumors.
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Malignant Solid Tumors
Keywords: MRG002
HX008
Antibody Drug Conjugate (ADC)
HER2
PD-1
Solid tumors
Lead sponsor: Shanghai Miracogen Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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 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.


Eligibility criteria: Inclusion Criteria:

1. Willing to sign the informed consent form and follow the requirements specified in the protocol.
2. Aged 18 to 75 (including 18 and 75), both genders.
3. Life expectancy ≥ 12 weeks.
4. 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).
5. The score of ECOG for performance status is 0 or 1.
6. The toxicity of previous anti-tumor treatment has recovered to ≤ Grade 1 as defined by NCI-CTCAEv5.0.
7. No severe cardiac dysfunction.
8. Organ functions must meet the basic requirements.
9. Cumulative dose of anthracycline ≤ 450 mg/m2 doxorubicin or its equivalent.

Exclusion Criteria:

1. Prior treatment with chemotherapy, biological therapy, immunotherapy, radiotherapy, investigational drugs, attenuated live vaccines, immunomodulators, CYP3A4 inhibitors/inducers, antibody-drug conjugates, etc.
2. Treatment with immune checkpoint inhibitors or tumor vaccines within 60 days prior to the first dose.
3. Treatment with systemic corticosteroids or other immunosuppressive drugs within 14 days prior to the first dose or during the study period.
4. History of severe cardiac disease.
5. Poorly controlled hypertension and hyperglycemia.
6. Presence of peripheral neuropathy ≥ Grade 2.
7. 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.
8. Central nervous system metastasis.
9. Received major surgery within 4 weeks prior to the first dose without complete recovery.
10. History of hypersensitivity to any component of MRG002 or HX008 or known history of hypersensitivity of ≥ Grade 3 to macromolecular protein products/monoclonal antibodies.
11. Evidence of active infection.
12. History of primary immunodeficiency or autoimmune disease.
13. 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.
14. Previous history of other primary malignancies.
15. Other conditions inappropriate for participation in this study, as deemed by the investigator.

Primary outcomes:
measure: Incidence of dose limiting toxicity (DLT) in each dose group
timeFrame: Within 28 days after the first dose.
measure: Adverse events
timeFrame: After signing informed consent until 90 days after the last dose.
measure: Recommended Phase II Dose (RP2D)
timeFrame: Baseline to study completion (up to 24 months)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Duration of Response (DOR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline to study completion (up to 24 months)
measure: Time to Response (TTR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Overall Survival (OS)
timeFrame: Baseline to study completion (up to 24 months)
measure: PK parameters: concentration-time curve
timeFrame: Baseline to 90 days after the last dose.
measure: Immunogenicity (ADA)
timeFrame: Baseline to 90 days after the last dose.
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Oriental Hospital
state: Shanghai
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Shanghai Oriental Hospital
name: Jin Li, MD
role: PRINCIPAL_INVESTIGATOR
References: