IMM2520, a PD-L1 and CD47 Bispecific Antibody in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This is a multi-center, open-label, dose-escalation and cohort-expansion phase I clinical study to evaluate the safety and tolerability, pharmacokinetics profile, efficacy and immunogenicity of IMM2520 in subjects with advanced solid tumors.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
IMM2520 is administered via intravenous infusion once week of cycle 1- 12 (4 weeks per cycle).
The accelerated titration method and the traditional "3+3" method will be adopted to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) in dose-escalation phase.
Once the RP2D is determined, Simon's two-stage design will be used to explore for each specific tumor cohort.adenocarcinoma/esophageal cancer, urothelial cancer, and/or others.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: IMM2520 in subjects with advanced solid tumors Dose-escalation phase: the dosing schedule of IMM2520 is 0.1 mg/kg, 0.4 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 4.0 mg/kg and 6.0 mg/kg sequentially. |
Drug: IMM2520
IMM2520 will be administered once a week intravenously at Day 1, Day8, Day 15 and Day 22 each cycle for up to 48 weeks.
Other Names:
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Outcome Measures
Primary Outcome Measures
- AEs, SAEs and DLT [From 1st dose of IMM2520 through 30 days after last dose]
Incidence and characteristics of adverse events (AEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs)
- MTD and RP2D [From start of treatment to treatment termination visit, up to 48weeks]
To determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of IMM2520 in subjects with advanced solid tumors.
- Overall Rate Response (ORR) [When the last subject enrolled completes approximately 48 weeks of treatment]
ORR is defined as the proportion of participants who have a partial response (PR) or critical response (CR)
- Disease Control Rate (DCR) [From start of treatment to the last subject enrolled completes approximately 48 weeks of treatment]
DCR is defined as the proportion of participants who have a critical response (CR), partial response (PR) or disease stable (SD)
- Duration of Response (DOR) [From start of treatment to the last subject enrolled completes approximately 48 weeks of treatment]
DOR is defined as time from date of initial documentation of a response (PR or CR) to date of first documented evidence of progressive disease (PD).
- Progression-free survival (PFS) [From start of treatment to treatment termination visit, up to 48 weeks]
Defined as the duration from the start of treatment until tumor progression or death of any cause
Secondary Outcome Measures
- Maximum Plasma Concentration (Cmax) [48 weeks of treatment cycles]
Maximum Plasma Concentration observed in patients with IMM2520 dosed
- time to maximum concentration (Tmax) [48 weeks of treatment cycles]
time to maximum concentration observed in patients with IMM2520 dosed
- Anti-drug antibody (ADA) [48 weeks of treatment cycles]
To evaluate the immunogenicity of IMM2520 in patients with malignancies
Eligibility Criteria
Criteria
Inclusion Criteria:
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The subjects must voluntarily sign the informed consent, and the subjects are willing and able to comply with the visits, treatment plans, laboratory assessments, and other requirements of the study.
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Age ≥18 years old.
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Patients who were diagnosed as advanced or metastatic solid tumors histologically or cytologically have failed previous standard treatments. Patient requires the treatment in the opinion of the investigator.
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There is at least one measurable tumor lesion (refer to RECIST 1.1), defined as the longest measurable diameter of non-lymph node lesions by imaging (CT/MRI) ≥10 mm or the short diameter of a single pathological lymph node lesion ≥15 mm; at least one evaluable tumor lesion is needed in the dose-escalation phase.
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With an expected survival of ≥ 12 weeks.
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Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (ECOG score of 0-2 is allowed for cohort-expansion phase).
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The organ or bone marrow function must meet the following laboratory criteria:
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Hematology: Absolute neutrophil count ≥ 1.5 × 109/L; hemoglobin ≥ 90 g/L; platelet count ≥ 75 × 109/L (without supportive treatment using granulocyte colony stimulating factor within 7 days before starting study treatment).
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Total serum bilirubin ≤ 1.5× upper limit of normal (ULN) (unless Gilbert syndrome is confirmed); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; ALT and AST ≤ 5.0×ULN in case of liver metastasis.
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Prothrombin time (PT) ≤ 1.2 × ULN, activated partial thromboplastin time (APTT) ≤ 1.2 × ULN; international normalized ratio (INR) ≤ 1.2 (unless the subject is receiving warfarin therapy). If the subject is taking oral anticoagulant therapy, the dose should be stable for 2 weeks; if the subject is taking oral warfarin, the subject's INR must be ≤ 2.5 without hemorrhage.
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Creatinine clearance (Cr) > 30 mL/min (Cockcroft and Gault Equation).
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Left ventricular ejection fraction (LVEF) ≥ 40%;
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Previously treated toxicities have recovered to Grade 1 [as per NCI CTCAE 5.0 grading criteria] (except toxicities which have no safety risk at the discretion of the investigator, such as alopecia, neurotoxicity ≤ Grade 2 caused by chemotherapeutic drugs, etc.).
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Females with childbearing potentials must be tested negative for serum pregnancy test during the screening period before receiving the first administration of IMM2520; any female patient with childbearing potential must agree to take effective contraceptive measures during the entire study and within 3 months after study completion. A patient is considered to have childbearing potential if he/she is biologically capable of having children and has a heterosexual sex life.
Exclusion Criteria:
A subject meeting any of the following criteria must be excluded from the study.
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Subjects are enrolled into another clinical study continuously, unless it is an observational, non-interfering clinical study or in the follow-up period of an interfering study.
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Treatment with the last systemic chemotherapy within 3 weeks; treatment with hormone therapy and small-molecule target therapy within 2 weeks; palliative radiation treatment for non-target lesions within 2 weeks; treatment with non-specific immunomodulatory therapy within 2 weeks prior to the first administration.
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Subjects with active central nervous system (CNS) metastases (Subjects with stable treated central nervous system [CNS] lesions who are off corticosteroid therapy for at least 2 weeks are not considered active).
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Subjects who have received previous treatment with > 1 PD-1 or PD-L1 inhibitors, such as pembrolizumab, nivolumab, atezolizumab or durvalumab.
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Subjects who have received previous treatment with anti-CD47 monoclonal antibody fusion protein.
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Subjects diagnosed with other malignancies within 2 years before the first dose with exceptions: a. cervical carcinoma in situ or basal or squamous cell carcinoma of the skin underwent radical resection; b. second primary carcinoma underwent radical resection and without recurrence within 5 years; c. double primary cancers that can benefit from this study in the opinion of the investigator.
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Subjects who received prior allogeneic hematopoietic stem cell transplant or other organ transplants with acute or chromic GVHD(graft versus host disease) requiring the long-term immunosuppressive therapy before 6 months of treatment.
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Subjects with active autoimmune diseases requiring systemic treatment (with glucocorticoids or immunosuppressive drugs) in the past 2 years with exceptions of hormone replacement therapy for thyroid disease, adrenal or pituitary insufficiency disease.
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Concurrent medical condition requiring systemic corticosteroids (prednisone daily dose
20 mg or equivalent dose) within14 days prior to first dose of the investigational product.
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Subjects who underwent a major surgery within 4 weeks prior to the first dose or planned to undergo a major surgery in 3 months after receiving the investigational drug (excluding catheterization, peripherally inserted central catheter, etc.).
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Hypertension , pulmonary hypertension or unstable angina, which cannot be controlled by medication; treatment with myocardial infarction, bypass or stent surgery within 6 months prior to administration; a history of chronic heart failure rated by the New York Heart Association (NYHA) as grade 3-4; severe arrhythmia requiring treatment (except for atrial fibrillation or paroxysmal supraventricular tachycardia that, according to the judgment of the investigators, do not affect the study); QTcF > 470 msec; history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to enrollment;
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A history of arterial thrombosis, deep venous thrombosis and pulmonary embolism within 3 months prior to the first administration.
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Subjects with diseases that may cause gastrointestinal bleeding or perforation;
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Concurrent interstitial lung disease (ILD) (except for radiation therapy-induced loco regional interstitial pneumonia), severe chronic obstructive pulmonary disease, severe pulmonary insufficiency.
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Subjects with thoracoabdominal or pericardial effusions that cannot be controlled by puncture and drainage and require repeated drainage or with significant symptoms.
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Subjects with uncontrollable serious active infection (such as sepsis, bacteremia, and viremia) within 4 weeks before the first administration, or subjects with any signs or symptoms of active infection within 2 weeks, or subjects requiring antibiotic treatment within 2 weeks (except for the preventive application of antibiotics); fever of unknown cause > 38.5℃ before the first dose (subjects with fever due to tumor can be included in the opinion of the subjects); active tuberculosis infection;
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A known history of serious allergy to PD-1/PD-L antibodies.
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Patients who received live attenuated vaccine within 4 weeks prior to the first dose of the investigational product, or plan to receive attenuated vaccine during the study.
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Patients with human immunodeficiency virus (HIV) infection, hepatitis B surface antigen (HBsAg) positive at screening, and HBV-DNA above the lower limit of measurement; HCV antibody positive at screening and HCV-RNA above the lower limit of measurement.
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Subjects with immune-related toxicity that leads to permanent drug discontinuation due to previous anti-tumor immunotherapy.
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History of psychiatric illness or substance abuse is likely to interfere with the ability to comply with protocol requirements or giving informed consent.
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Other situations where investigators believe they are inappropriate for participation in this study
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
- Shandong Cancer Hospital and Institute
Investigators
- Principal Investigator: Yuping Sun, Shandong Cancer Hospital and Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IMM2520-001