Clinical Trials /

LZM009 to Treat Patients With Advanced Solid Tumors

NCT03286296

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: LZM009 to Treat Patients With Advanced Solid Tumors
  • Official Title: A First-in-Human, Multicenter, Open-label, Phase 1 Dose-Escalation Study of LZM009 in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: LZM009-001
  • NCT ID: NCT03286296

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
LZM009,recombinant humanized anti-PD-1 monoclonal antibody for injectionLZM009

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
LZM009Experimental
  • LZM009,recombinant humanized anti-PD-1 monoclonal antibody for injection

Eligibility Criteria

        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 exclusion
        criteria listed below:

          1. Receiving concurrent anti-cancer therapy or investigational therapy (chemotherapy,
             radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy,
             biologic therapy, (with the exception of hormones for hypothyroidism, estrogen
             replacement therapy, or LHRH agonists required to suppress serum testosterone levels).

          2. Patients who have experienced a Grade 3 or higher toxicity related to prior PD-1/PD-L1
             treatment.

          3. Prior anticancer therapy less than 21 days of study entry, or 5 half-lives, whichever
             is shorter.

          4. Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of
             study drug.

          5. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not
             recover to ≤ Grade 1.

          6. Known bleeding diathesis/disorder unless controlled.

          7. Recent history of non-chemotherapy induced thrombocytopenia associated bleeding within
             1 year prior to first dose of study drug.

          8. Have active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia
             (AHA), or a history of being refractory to platelet transfusions (within 1 year prior
             to the first dose of study drug).

          9. Serious gastrointestinal bleeding within 3 months.

         10. Received a biologic (G-CSF, GM-CSF or erythropoietin) within 28 days prior to the
             first dose of study drug and within 28 days after the first dose.

         11. Patients with a condition requiring systemic treatment with either corticosteroids
             (>10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14
             days before the planned first dose of study drug. Inhaled or topical steroids, and
             adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in
             the absence of active autoimmune disease. Ophthalmologic, nasal and intra-articular
             injections or steroids are acceptable.

         12. Failure to recover adequately, as judged by the investigator, from prior surgical
             procedures. Patients who have had major surgery within 28 days from study entry, and
             patients who have had minor surgery within 14 days of study entry.

         13. Unstable angina, myocardial infarction, or a coronary revascularization procedure
             within 180 days of study entry.

         14. Neurologic instability per clinical evaluation due to tumor involvement of the central
             nervous system (CNS). Patients with CNS tumors that have been treated, are
             asymptomatic and who have discontinued steroids (for the treatment of CNS tumors)
             for>28 days may be enrolled.

         15. Positive laboratory test for HBsAg or anti-HCV. Patients with anti-hepatitis B core
             antibody are eligible if negative for HBsAg; patients positive for anti-HCV may be
             enrolled if negative by nucleic acid amplification test.

         16. Has a history of human immunodeficiency virus (HIV) antibody positive, or tests
             positive for HIV at screening.

         17. Any diagnosis of autoimmune disease. Subjects with hypothyroidism stable on hormone
             replacement, adrenal insufficiency on steroid replacement, skin disorders (such as
             vitiligo, psoriasis or alopecia) not requiring systemic treatment are permitted to
             enroll.

         18. Grade 3 or higher pneumonitis or neuropathy during previous treatment with
             immunotherapy.

         19. Diagnosis of fever and neutropenia within 1 week prior to study drug administration.

         20. Uncontrolled concurrent illness including, but not limited to: serious uncontrolled
             diabetes (blood glucose > 250 mg/dL), symptomatic congestive heart failure, unstable
             angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
             would limit compliance with the study requirements.

         21. Patient has received a live, attenuated vaccine within 28 days of planned start of
             study therapy.

         22. Known allergies, hypersensitivity, or intolerance to protein-based therapies or with a
             history of any significant drug allergy (e.g., anaphylaxis, hepatotoxicity,
             immune-mediated thrombocytopenia or anemia), or to LZM009 recipients (refer to
             Investigator's Brochure).

         23. Currently participating and receiving study therapy or has participated in a study of
             an investigational agent and received study therapy or used an investigational device
             within 21 days or 5 half-lives, whichever is shorter, before the start of study
             treatment, the exception of participants in the follow-up phase.

         24. Any other condition or circumstance of that would, in the opinion of the investigator,
             make the patient unsuitable for participation in the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine number of patients experiencing dose limiting toxicities
Time Frame:Day 1 through Day 28
Safety Issue:
Description:And frequency and severity of DLT at LZM009 doses of 1mg/kg, 3mkg/kg and 10mkg/kg at 28 days after the first dose.

Secondary Outcome Measures

Measure:Characterize the pharmacokinetics (PK) profiles of LZM009 in blood specimens of subjects with at least 1 dose
Time Frame: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).
Safety Issue:
Description:
Measure:Characterize the immunogenicity profiles of LZM009 in blood specimens of subjects with at least 1 dose
Time Frame: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).
Safety Issue:
Description:Presence of anti-LZM009 antibodies/neutralizing anti-LZM009 antibodies (nAbs) and effect on PK of LZM009.
Measure:Assess preliminary anti-tumor activity of LZM009 in subjects with advanced solid tumors
Time Frame:17 months
Safety Issue:
Description:Overall response rate (ORR) by the Response Criteria in Solid Tumors (RECIST) v1.1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Livzon Pharmaceutical Group Inc.

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