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.
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.
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
3. Prior anticancer therapy less than 21 days of study entry, or 5 half-lives, whichever
4. Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of
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
18. Grade 3 or higher pneumonitis or neuropathy during previous treatment with
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
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
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.