A Phase 1/2 Study of 7MW3711 in Advanced Solid Tumors

Study Overview
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Brief Summary
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7MW3711 is an antibody-drug conjugate(ADC) directed to a target wildly expressed on solid tumors. This is an open-label, multicenter, phase 1/2 study to evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 7MW3711 in subjects with advanced solid tumors.

Detailed Description
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Two parts are included in this study. The part of dose escalation and dose expansion(part 1) will enrolled subjects with advanced solid tumors and is to evaluate the safety and tolerability and to determine the maximum tolerated dose and/or the recommend phase 2 dose(RP2D) of 7MW3711 in subjects with advanced solid tumors.

Official Title
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A Phase Ⅰ/Ⅱ Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 7MW3711 in Subjects With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: 7MW3711 for injection
* Drug: 7MW3711 for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Life expectancy of at least 3 months as assessed by the Investigator. Histologically or cytologically confirmed locally advanced or metastatic solid tumor, progressive after last treatment received and who progressed on or after standard therapies or intolerant to approved therapies or who lack of effient standard therapies. An archival tumor tissue sample(formalin-fixed paraffin-embedded (FFPE) tumor tissue block or at least 5 unstained slides) or a fresh tissue sample should be provided. If the tissue sample cannot be provided during dose escalation, enrollment into the study is allowed after discussion with the Investigator Measurable or evaluable disease by RECIST v1.1. Have adequate hematopoietic, renal and hepatic functions. Men or women willing to use adequate contraceptive measures throughout the study. Exclusion Criteria: Have other prior malignancies within 3 years before the first administration. Known central nervous system metastatic disease or carcinomatous meningitis except for treated and stable brain metastases. Have significant, uncontrolled, or active cardiovascular disease. Known history of COPD, or intestinal lung disease, or other respiratory diseases requring inpatient treatments within 4 weeks prior to first administration. Have adverse events due to prior antitumor therapy not resolved to grade 1 or lower by NCI CTCAE V5.0. Have active infections requiring treatment within 14 weeks; have infection of HIV, active infection of HCV and HBV. Prior treatment with an antibody drug conjugate (ADC) that consists of an topoisomerase I inhibitor. Prior treatment with B7-H3 targeted agents. Have received chemotherapy, immunotherapy, curative radiation within 3 weeks prior to the first administration or targeted molecular within 2 weeks prior to first administration. have received Chinese patent medicine or Chinese herbs of anti-tumor indications within 1 weeks prior to the first administration. Have received any systemic immunosuppressants within 2 weeks prior to the first administration except for topical corticosteroids. Have received any other investigational drugs or medical device within 4 weeks prior to the first administration. History of drug abuse including narcotic and psychiatric drugs within 12 months prior to screening. Pregnant, or nursing females.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation and dose expansion<br>All subjects enrolled in the part of dose escalation and dose expansion will receive 7MW3711 by introvenous infusion | Drug: 7MW3711 for injection<br>* IV administration of 7MW3711, Q3W, 3 weeks a cycle<br>|
| Experimental: Cohort expansion<br>All subjects enrolled in the part of cohort expansion will be treated by 7MW3711 will receive 7MW3711 by introvenous infusion | Drug: 7MW3711 for injection<br>* IV administration of 7MW3711, the dosage regimen including dosage and dosing frequency for cohort expansion is conformed on basis of the data in part 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluation of the incidence of adverse events (AEs) (part 1) | Incidence and seriousness of adverse events (AEs) and serious adverse events (SAEs) by CTCAE version 5.0 | approximately up to 16 cycles, 21 days a cycle | 
| Identification of the MTD and /or RP2D of 7MW3711(part 1) | MTD(maximum tolerated dose) and /or RP2D(recommended phase II dose)of 7MW3711(part 1) | from Day1 to Day21 in cycle1 of part 1 | 
| Overall response rate (ORR) evaluated by investigators based on RECIST version 1.1 in selected solid tumors(part 2) | ORR:defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR) | approximately up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate (ORR) (part1) | ORR:defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR) based on RECIST version 1.1 | approximately up to 1 year | 
| evaluation of the incidence of adverse events (AEs) (part 2) | Incidence and seriousness of adverse events (AEs) and serious adverse events (SAEs) by CTCAE version 5.0 | approximately up to 2 years | 
| evaluation of Peak Plasma Concentration (Cmax) of 7MW3711 | Peak Plasma Concentration（Cmax） | approximately up to 2 years | 
| evaluation of AUC of 7MW3711 | Area under the plasma concentration versus time curve (AUC) | approximately up to 2 years | 
| evaluation of t1/2 of 7MW3711 | Half life time（t1/2） | approximately up to 2 years |