A Clinical Study of MIL95 in Advanced Malignancies.

Study Overview
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Brief Summary
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This study is composed of two stages: Part A initial dose escalation and Part B maintenance dose escalation. Both parts will adopt the classical 3+3 dose escalation design. The starting dose for phase Ia part A is 0.1 mg/kg QW, followed by 3 dose cohorts (0.3mg/kg QW, 0.8mg/kg QW and 1mg/kg QW). Duration of dose limiting toxicity (DLT) observation is 14 days. Part B will have 5 dose cohorts(3mg/kg QW, 10mg/kg QW, 20mg/kg QW 30mg/kg QW and 45mg/kg QW). DLT observation period is 28 days. The subject number for each cohort in Part B will be increased to 6 if the subject number enrolled in each cohort is less than 6.

Official Title
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A Phase I Clinical Study of Recombinant Humanized Monoclonal Antibody MIL95 Injection in the Treatment of Lymphomas and Advanced Malignant Solid Tumors

Conditions
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Advanced Malignancies

Intervention / Treatment
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* Drug: Recombinant Humanized Monoclonal Antibody MIL95


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >=18 years of age; Diagnosis of Refractory/relapsed lymphomas or solid tumor; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Life expectancy >=3 months; Sufficient organ and bone marrow function; At least one measurable lesion or evaluable lesion (recist v1.1 or Lugano 2014); Able and willing to provide written informed consent and to comply with the study protocol. Exclusion Criteria: Prior use of any anti-cancer therapy(including chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc) within 4 weeks of study start; Previous exposure to any drug targeting CD47 or SIRPα; Major surgery within 4 weeks prior to the first administration or expected to undergo major surgery during the study treatment; Live attenuated vaccine administrated within 4 weeks before the first administration or during the study period; Central nervous system metastasis; History of other primary malignant tumors in 5 years; Evidence of significant, uncontrolled concomitant disease; Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C(including HBsAg,HBcAb positive with abnormal HBV DNA or HCV RNA ); Active or suspected autoimmune diseases; Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) while participating in the study; 2) for at least 12 months after discontinuation of all study treatments; Known history of hemolytic anemia; Known severe allergic reaction or/and infusion reaction to monoclonal antibody.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIL95<br> | Drug: Recombinant Humanized Monoclonal Antibody MIL95<br>* PART A :The patients confirming to the eligibility criteria will be assigned to the 4 dose groups (0.1mg/kg, 0.3mg/kg, 0.8mg/kg, 1.0mg/kg, respectively) based on the sequence of inclusion. Each patient will receive an intravenous infusion of MIL95 every week on Day 1 for a maximum of Twelve weeks. PART B:One recommended dose as a priming dose will be selected from 4 dose groups(0.1mg/kg、0.3mg/kg、0.8mg/kg、1.0mg/kg) based on results of PART A. Each patient will receive a priming dose of MIL95 on Day 1 Cycle 1.The patients will be assigned to the 5 maintenance dose groups (3mg/kg, 10mg/kg, 20mg/kg, 30mg/kg, 45mg/kg, respectively) based on the sequence of inclusion. The maintenance dose was given on Day 8,15,22 Cycle 1 and on Day 1,8,15,22 Cycle 2+. Each cycle was 28 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events | Percentage of Participants with AEs and SAEs assessed by NCI CTCAE v5.0. | up to 1year after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics:AUC | The area under the curve (AUC) of serum concentration of the drug after the administration | up to 1year after enrollment | 
| Pharmacokinetics: Cmax | Maximum concentration(Cmax) of the drug after administration | up to 1year after enrollment | 
| Objective response rate (ORR) | To evaluate preliminary anti-tumor activity of MIL95 in subjects with advanced malignancies.ORR includes complete remission(CR) and partial remission(PR) assessed by RECIST v1.1 criteria for solid tumors and Lugano2014 criteria for lymphoma. | up to 1year after enrollment | 
| Duration of response (DoR) | DOR is defined as the time from the initial response (CR or PR) to the time of disease progression or death, whichever occurs first. | up to 1year after enrollment | 
| Progression free survival (PFS) | Defined as the time from the first day of study treatment to disease progression or death, whichever occurs first. | up to 1year after enrollment | 
| Immunogenicity | Anti-Drug Antibodies (ADA) will be tested and percentage of ADA positive patients will be calculated to evaluate immunogenicity of MIL95. | up to 1year after enrollment |