Advanced Malignancies
Conditions
Brief summary
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.
Interventions
DRUGRecombinant Humanized Monoclonal Antibody MIL95
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.
Sponsors
Beijing Mabworks Biotech Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients, \>=18 years of age; 2. Diagnosis of Refractory/relapsed lymphomas or solid tumor; 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 4. Life expectancy \>=3 months; 5. Sufficient organ and bone marrow function; 6. At least one measurable lesion or evaluable lesion (recist v1.1 or Lugano 2014); 7. Able and willing to provide written informed consent and to comply with the study protocol.
Exclusion criteria
1. Prior use of any anti-cancer therapy(including chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc) within 4 weeks of study start; 2. Previous exposure to any drug targeting CD47 or SIRPα; 3. Major surgery within 4 weeks prior to the first administration or expected to undergo major surgery during the study treatment; 4. Live attenuated vaccine administrated within 4 weeks before the first administration or during the study period; 5. Central nervous system metastasis; 6. History of other primary malignant tumors in 5 years; 7. Evidence of significant, uncontrolled concomitant disease; 8. Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C(including HBsAg,HBcAb positive with abnormal HBV DNA or HCV RNA ); 9. Active or suspected autoimmune diseases; 10. 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; 11. Known history of hemolytic anemia; 12. Known severe allergic reaction or/and infusion reaction to monoclonal antibody.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Adverse Events | up to 1year after enrollment | Percentage of Participants with AEs and SAEs assessed by NCI CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Cmax | up to 1year after enrollment | Maximum concentration(Cmax) of the drug after administration |
| Objective response rate (ORR) | up to 1year after enrollment | 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. |
| Pharmacokinetics:AUC | up to 1year after enrollment | The area under the curve (AUC) of serum concentration of the drug after the administration |
| Progression free survival (PFS) | up to 1year after enrollment | Defined as the time from the first day of study treatment to disease progression or death, whichever occurs first. |
| Immunogenicity | up to 1year after enrollment | Anti-Drug Antibodies (ADA) will be tested and percentage of ADA positive patients will be calculated to evaluate immunogenicity of MIL95. |
| Duration of response (DoR) | up to 1year after enrollment | DOR is defined as the time from the initial response (CR or PR) to the time of disease progression or death, whichever occurs first. |
Countries
China
Contacts
Primary ContactYuqin Song, doctor
Outcome results
None listed