A Phase I, First-in-Human, Dose-Escalation Study to Evaluate the Safety of the Monoclonal
Antibody PTX-35 in Patients with Advanced Solid Tumors Refractory to Standard of Care
This is an open-label, single arm, first-in-human, Phase I study of intravenous
administration of PTX-35 to patients with advanced solid tumors refractory to, or ineligible
for, or who refuse available SOC. Five escalating dose levels of PTX-35 will be explored
using a traditional 3+3 design based on dose-limiting toxicities (DLTs) until optimal
immunological dose (OID) or maximum tolerated dose (MTD) is established.
In order to participate in this study, a patient must:
1. Be willing and have the capacity to sign the written informed consent form.
2. Be male or female of at least 18 years of age at the time of signing informed consent.
3. Have a documented diagnosis of metastatic or advanced, unresectable solid tumor
disease. Patient must have progressed or recurred following standard of care (SOC)
therapies, or are ineligible for, or who refuse other safe and effective SOC
therapies, and whom the Investigator believes may benefit from experimental treatment
4. Have an acceptable organ function, as defined below:
1. Albumin ≥ 2.5 g/dL
2. Total bilirubin < 3.0 × upper limit of normal (ULN), unless patient has Gilbert's
3. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 × ULN, or
- 5 × ULN in the case of liver metastases
4. Calculated or measured creatinine clearance > 35 mL/minute per the
5. Absolute neutrophil count ≥ 1,500/mm3
6. Hemoglobin ≥ 9 g/dL
7. Platelet count ≥ 100,000/mm3
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
6. Have life expectancy of at least three months.
7. Patients, both females and males, of childbearing/reproductive potential must agree to
use adequate contraception while included in the trial and for six months after the
last treatment with PTX-35.
In order to participate in this study, a patient must not:
1. Have received any systemic anticancer therapy including small molecules, chemotherapy,
radiation therapy, monoclonal antibodies or any other experimental drug within 4 weeks
of first dose of PTX-35. Adjuvant anti hormonal treatment(s) for prior breast cancer
or prostate cancer are allowed. (Note: washout for palliative radiation therapy is 2
2. Have clinically significant cardiac disease, including:
1. Onset of unstable angina within 6 months of signing the Informed Consent Form
2. Acute myocardial infarction within 6 months of the signing the ICF.
3. Known congestive heart failure (Grade III or IV as classified by the New York
Heart Association); and/ or a known decreased cardiac ejection fraction (LVEF) of
4. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or
diastolic blood pressure ≥ 100 mmHg, despite optimal medical management.
3. Have known or clinically suspected leptomeningeal disease. Stable, previously treated
metastases in the brain or spinal cord, are allowed as long as these are considered
stable (by CT or MRI), and not requiring systemic corticosteroids.
4. Have a history of ≥ Grade 3 allergic reactions, or suspected allergy or intolerance to
monoclonal antibody therapies.
5. Have a history of suspected cytokine release syndrome (CRS).
6. Have any known immunodeficiency disorders (testing not required).
7. Have received prior allogeneic stem cell transplant.
8. Have ongoing or current autoimmune disease. Permanent but stable and manageable immune
related adverse events (irAE) from prior therapies are permissible, if prednisone
equivalent corticosteroid use does not exceed 10 mg/day.
9. Have any other condition requiring concurrent systemic immunosuppressive therapy
(other than allowable exceptions which do not exceed 10mg/day of
10. Have clinically significant active viral, bacterial or fungal infection requiring:
1. Intravenous treatment with antimicrobial therapy completed less than two weeks
prior to first dose, or
2. Oral treatment with antimicrobial therapy completed less than one week prior to
first dose. Prophylactic treatment with antibiotics (e.g. for dental extractions)
11. Have had major surgery (requiring general anesthesia or inpatient hospitalization)
within four weeks before first administration of PTX-35.
12. Have had a known tetanus/diphtheria vaccine within the past 10 years.
13. Have known additional malignancy that is active and/or progressive requiring
treatment; exceptions include basal cell or squamous cell skin cancer, in situ
cervical cancer, or other cancer for which the patient has been disease-free for at
least two years.
14. Have known previously untreated or symptomatic metastases in the brain or spinal cord
requiring steroids. Patients with treated and stable CNS metastases may be enrolled
after approval of the sponsor and/or Medical Monitor.
15. Have any other ongoing significant, uncontrolled medical condition in the opinion of
16. Have known positive serology for human immunodeficiency virus (HIV), hepatitis B, or
hepatitis C (except in cases of immunity after cured infection). Testing not required.
17. Have a history of substance abuse, medical, psychological or social conditions that
may interfere with the patient's participation in the trial or evaluation of the trial
18. Be a female patient who is pregnant or breast feeding.