Solid Tumor
Conditions
Brief summary
To assess the safety and tolerability of IV administered LZM009 in subjects with advanced solid tumors who have progressed or are non-responsive to available therapies.
Interventions
BIOLOGICALLZM009,recombinant humanized anti-PD-1 monoclonal antibody for injection
LZM009 doses of 1, 3, and 10 mg/kg will be administrated intravenously on day 1 and 29 and every 3 weeks thereafter until disease progression or intolerable toxicity, withdrawal of consent, or end of study
Sponsors
Livzon Pharmaceutical Group Inc.
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
Patients must meet all of the following inclusion criteria to be eligible for participation in this study: 1. Histologically or cytologically confirmed solid malignancy. 2. Male or non-pregnant, non-lactating female patients age ≥18 years. 3. Locally advanced or metastatic disease that is refractory to standard therapy \[note for patients with NSCLC patients with activating ALK translocation or EGFR mutations must have been treated and failed appropriate therapy\], or for which there is no standard available therapy. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2. 5. Subject with a life expectancy of ≥ 12 weeks. 6. Adequate hematologic function as indicated by 1. Platelet count ≥ 100,000/mm3 2. Hemoglobin ≥ 9.0g/dL 3. Absolute neutrophil count (ANC) ≥1000/uL Note: Use of growth-factors to maintain ANC criterion (within 28 days prior to the first dose of study drug and within 28 days after day 1 of Cycle 1) is not permitted. 7. Adequate renal and liver function as indicated by: 1. Serum creatinine ≤ 1.5 x upper limit of normal (ULN); if serum creatinine is \>1.5 x ULN, creatinine clearance must be ≥ 50 mL/min either by calculation or by measured 24-hour urine collection 2. Total bilirubin ≤1.5 x ULN; If Gilbert's Syndrome may have Bilirubin\> 1.5 x ULN 3. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤3 x ULN of institution's normal range; for patients with known liver metastases, AST and ALT may be ≤ 5 x ULN. 4. Coagulation: aPTT and PT≤ 1.3 x ULN 8. Patients with brain metastases are eligible if clinically controlled that is defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function & no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug. 9. Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential (postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug. 10. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures). 11. Willingness and ability to comply with study procedures and follow-up examination.
Exclusion criteria
To be eligible for entry into the study, the subject must not meet any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine number of patients experiencing dose limiting toxicities | Day 1 through Day 28 | And frequency and severity of DLT at LZM009 doses of 1mg/kg, 3mkg/kg and 10mkg/kg at 28 days after the first dose. |
| Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) | 17 months | Determination of MTD and RP2D is dependent on number of cohorts and patients experiencing DLT. |
| Number of patients experiencing clinical or laboratory adverse events as a measure of safety and tolerability | Screening to 28 days after last treatment administration, or until drug related toxicities have resolved, whichever is later; or earlier than 28 days should the patient commence another anti-cancer therapy in the meantime, approximately 17 weeks. | Safety variables include incidence and severity of treatment emergent adverse events (TEAEs) and immune-related AEs (irAEs), vital signs measurements, clinical laboratory values and ECGs as determined by CTCAEv4.03. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the pharmacokinetics (PK) profiles of LZM009 in blood specimens of subjects with at least 1 dose | Predose, 0 h, 2 h, 6h, 24h, days 3, 8, 15 and 22 post infusion of cycle 1; predose of cycle 2 and 3; pre-dose, 0 h, 2 h, 6h, days 8, and 15 post infusion of cycle 4 and predose of every other cycle after Cycle 5(one cycle=21 days except Cycle 1=28 days). | — |
| Characterize the immunogenicity profiles of LZM009 in blood specimens of subjects with at least 1 dose | Predose on C1D1, C2D1, C4D1, and at predose of every other cycle after Cycle 5, thereafter for the first 12 months, and 28 days after the last dose(one cycle=21 days except Cycle 1=28 days). | Presence of anti-LZM009 antibodies/neutralizing anti-LZM009 antibodies (nAbs) and effect on PK of LZM009. |
| Assess preliminary anti-tumor activity of LZM009 in subjects with advanced solid tumors | 17 months | Overall response rate (ORR) by the Response Criteria in Solid Tumors (RECIST) v1.1. |
Countries
United States
Outcome results
None listed