A Phase I Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity o f Ascending Doses of PT0I (Pegtomarginase) in Subjects With Advanced Malignancies

Athenex, Inc.1 site in 1 country62 target enrollmentApril 21, 2021

ConditionsAdvanced Solid Malignancies

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Advanced Solid Malignancies
Sponsor: Athenex, Inc.
Enrollment: 62
Locations: 1
Primary Endpoint: Number of participants with treatment-related adverse events as assessed by CTCAE v4.3 criteria.
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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.'

Detailed Description

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.

Registry

clinicaltrials.gov

Start Date

April 21, 2021

End Date

December 1, 2022

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Athenex, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Eligible subjects must have/be:
•Able to understand and voluntarily sign an informed consent form (ICF)
•Male and female adults ≥18 years of age at the time of informed consent
•Advanced solid malignancies for which no standard therapy is available. Subjects in whom available standard therapy is contraindicated may be eligible.
•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.
•At least 1 measurable site of disease as defined per RECIST v1.1 criteria (Dose Expansion Phase) or evaluable disease (Dose Escalation Phase only)
•Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1
•Life expectancy of \>12 weeks
•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:

Exclusion Criteria

•Eligible subjects must not have/be:
•Received prior arginase or arginine deiminase therapy
•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
•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
•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
•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

Outcomes

Primary Outcomes

Number of participants with treatment-related adverse events as assessed by CTCAE v4.3 criteria.

Time Frame: Day 1 up to 30 days post last dose

Number of participants with treatment related changes from baseline in vital signs, laboratory parameters and 12-lead ECG findings.

The maximum tolerated dose (MTD), and/or recommended Phase 2 dose (RP2D) together with the biologically effective dose (BED) of PT01.

Time Frame: 4 weeks

Dose-limiting toxicity (DLT) for determination of MTD and/or RP2D. The grading of toxicity is based on the NCI CTCAE v4.03 criteria. Reduction and duration of arginine for determination of BED

Secondary Outcomes

Area Under Plasma Concentration-Time Curve (AUC)(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post dose.)
The elimination half-life (t1/2) of PT01(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post infusion.)
The volume of PT01 distribution (Vd) in plasma.(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post infusion.)
The amount of PT01present at the maximum concentration in plasma (Tmax)(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post infusion.)
The time of last quantifiable presence of PT01 in plasma(Tlast)(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post infusion.)
Maximum Observed Plasma Concentration (Cmax) of PT01(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post infusion.)
The absolute-percent of arginine reduction from baseline(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post infusion)
The preliminary activity of PT01 by evaluating tumor response.(8 weeks)
PT01 concentration at the end of a dosing interval, immediately before next administration (Ctrough), the lowest observed concentration.(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post infusion.)
The total clearance of the PT01 from plasma (CL)(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post infusion)
Duration of arginine reduction <10% of baseline.(Cycle 0 Day 1: predose PT01 (Hour 0) and at 0.5 (end of infusion), 2, 4, 8, 24, 48, 72, 168, and 240 hours after the start of the PT01 IV infusion. Cycle 1 and Beyond, prepose and .5 hour post infusion.)