This is a first-in-human (FIH) Phase 1 dose escalation study to evaluate the safety,
tolerability, PK, PD, and preliminary activity of PT01 administered IV in subjects with
advanced malignancies.'
The study consists of a Dose Escalation Phase and a Dose Expansion Phase, both of which
include a 28-day Screening Period, Baseline, a Treatment Period (comprised of 28-day cycles
with weekly dosing on Days 1, 8, 15, and 22), and a Follow-up Period. Unique to the Dose
Escalation Phase is the inclusion of Cycle 0 during which a single dose of PT01 will be
administered before Cycle 1 for detailed exploration of the PK/PD relationship.
All PT01 IV doses will be administered at the clinical site.
Inclusion Criteria:
Eligible subjects must have/be:
1. Able to understand and voluntarily sign an informed consent form (ICF)
2. Male and female adults ≥18 years of age at the time of informed consent
3. Advanced solid malignancies for which no standard therapy is available. Subjects in
whom available standard therapy is contraindicated may be eligible.
4. For Dose Expansion Phase:
• Expansion Group A: Histologically confirmed unresectable locally advanced or
metastatic (AJCC stage IIIB, IIIC, or IV) cutaneous malignant melanoma for which no
standard therapy is suitable.
5. At least 1 measurable site of disease as defined per RECIST v1.1 criteria (Dose
Expansion Phase) or evaluable disease (Dose Escalation Phase only)
6. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
7. Life expectancy of >12 weeks
8. Adequate hematologic status within 28 days prior to dosing as demonstrated by not
requiring transfusion support or granulocyte-colony stimulating factor (G-CSF) to
maintain:
- Absolute neutrophil count (ANC) ≥1.5 × 109/L
- Platelet count ≥100 × 109/L
- Hemoglobin ≥90 g/L
9. Adequate liver function as demonstrated by:
- Serum bilirubin <2 × the upper limit of normal (ULN)
- Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤3 × ULN or ≤5 ×
ULN in subjects with liver metastases
- Gamma-glutamyl transferase ≤5 × ULN Athenex, Inc. Confidential Page 9 Final
v2.0_17 Jun 2019 Clinical Study Protocol_Amendment 01 ATX-PT01-001
- Alkaline phosphatase ≤3 × ULN or ≤5 × ULN if bone or liver metastasis is present
10. Serum creatinine ≤1.5 × ULN or estimated creatinine clearance ≥50 mL/min according to
the Cockcroft-Gault formula
11. Prothrombin time(PT) (or International Normalized Ratio[INR]) and activated partial
thromboplastin time (aPTT) ≤1.5 × ULN or within the intended therapeutic range within
72 hours before the first dose of study drug in subjects receiving anticoagulant
therapy
12. Willing and able to comply with scheduled visits, treatment plan, and laboratory tests
13. Absence of any other malignancy which has been active or treated within the past 3
years, except for cervical intraepithelial neoplasia, and nonmelanoma skin cancers
(basal cell and squamous cell carcinomas)
14. Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis)
OR agree to use a condom with spermicide and to not donate sperm during the study and
for at least 90 days following last dose of PT01
15. Female subjects must be postmenopausal (>12 months without menses) or surgically
sterile (ie,by hysterectomy and/or bilateral oophorectomy) or must be using highly
effective contraception (ie, oral contraceptives, intrauterine device, double barrier
method of condom and spermicide) and agree to continue use of contraception for 90
days after their last dose of PT01
16. Subjects who are of childbearing potential must have a negative serum pregnancy test
at Screening and within 72 hours prior to the first dose
17. Peripheral forearm veins suitable for venous access including cannulation for infusion
of PT01 and multiple blood sampling
Exclusion Criteria:
Eligible subjects must not have/be:
1. Received prior arginase or arginine deiminase therapy
2. Received recent anticancer therapy defined by:
- Chemotherapy, immunotherapy, hormonal therapy, and monoclonal antibodies (but
excluding nitrosourea, mitomycin-C, targeted therapy) ≤28 days prior to starting
study drug or who have not recovered from side effects of such therapy to Grade≤1
(National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events
[CTCAE] v4.03) except for subjects with alopecia; subjects receiving luteinizing
hormone-releasing hormone agonists may be considered for enrollment after
discussion with the Sponsor
- Last administration of nitrosourea or mitomycin-C ≤42 days prior to starting
study drug or who have not recovered from the side effects of such therapy to
Grade ≤1
- Targeted therapy (eg, sunitinib, sorafenib, pazopanib) ≤14 days prior to starting
study drug, or who have not recovered from the side effects of such therapy to
Grade ≤1
- Radiotherapy ≤28 days prior to starting study drug or ≤14 days prior to starting
study drug in the case of localized radiotherapy (eg, for analgesic purpose or
for lytic lesions at risk of fracture) or who have not recovered from
radiotherapy toxicities to Grade ≤1
3. Undergone major surgery (eg, intrathoracic, intraabdominal, or intrapelvic), open
biopsy, or significant traumatic injury ≤28 days prior to starting study treatment;
subjects who have had minor procedures, percutaneous biopsies, or placement of
vascular access device ≤7 days prior to starting study drug; or subjects who have not
recovered from side effects of such procedure or injury
4. Uncontrolled concurrent illness including, but not limited to, ongoing or active
serious infection Athenex, Inc. Confidential Page 10 Final v2.0_17 Jun 2019 Clinical
Study Protocol_Amendment 01 ATX-PT01-001 requiring systemic antimicrobials (within 14
days prior to first dose), uncontrolled arterial hypertension (>160/100 mm Hg on
antihypertensive medications), chronic pulmonary disease requiring oxygen, known
bleeding disorders, uncontrolled endocrine diseases, altered mental status, or
psychiatric illness/social situations that would limit compliance with protocol
requirements
5. Significant cardiac or pulmonary disease defined by New York Heart Association Class
III or IV, history of myocardial infarction within 6 months prior starting study drug,
significant unstable arrhythmia, or evidence of ischemia on ECG
6. Symptomatic or uncontrolled brain metastases requiring current treatment (fewer than
28 days from last cranial radiation or from last steroids use)
7. Healing or open wound(s)
8. Lack of recovery of prior AEs to Grade ≤1 severity (except alopecia or lymphopenia)
due to medications administered prior to the first dose of study drug
9. Any other condition or finding (including social situation) that, in the opinion of
the Investigator, may render the subject to be either at excessive risk for treatment
complications or not able to provide evaluable outcome information
10. Pregnantorbreast-feedingwomen
11. Known allergy to any of the formulation components of PT01