A Phase I Open-label Study for Subjects With Advanced Malignancies

NCT04136834 | Unknown Phase 1 FDA Drug

• 1 other identifier: ATX-PT01-001
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 3

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.'

Conditions

Advanced Solid Malignancies

Outcome Measures

Primary Outcomes (2)

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

  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

  4 weeks

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

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

  Day 1 up to 30 days post last dose

Secondary Outcomes (11)

• 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.

• 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 preliminary activity of PT01 by evaluating tumor response.

  8 weeks

• 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 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.

Study Arms (1)

Pegtomarginase (PT01)

EXPERIMENTAL

To determine the MTD of PT01 based on the toxicity observed during Cycle 1 of the Dose Escalation Phase and to investigate the safety and tolerability of PT01 when administered intravenously(IV) to subjects with advanced malignancies

Biological: PT01 (Pegtomarginase)

Interventions

PT01 (Pegtomarginase) BIOLOGICAL

PT01 (Pegtomarginase) breaks down arginine in the blood stream, reducing the supply of arginine and stopping the cancer cells from growing. Normal cells can continue to make their own arginine inside the cell, so PT01 targets the rapidly growing cancer cells.

Pegtomarginase (PT01)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Absolute neutrophil count (ANC) ≥1.5 × 109/L
• Platelet count ≥100 × 109/L
• Hemoglobin ≥90 g/L
• Adequate liver function as demonstrated by:
• Serum bilirubin \<2 × the upper limit of normal (ULN)

You may not qualify if:

• 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
• Symptomatic or uncontrolled brain metastases requiring current treatment (fewer than 28 days from last cranial radiation or from last steroids use)
• Healing or open wound(s)
• 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
• 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
• Pregnantorbreast-feedingwomen

Sponsors & Collaborators

• Athenex, Inc.: lead

Study Sites (3)

Mayo Clinic

Phoenix, Arizona, 85054, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Central Study Contacts

Donna Madore

CONTACT

5088264444; ext-dmadore@athenex.com

Jane DeVane

CONTACT

908-272-0274; jdevane@athenex.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: October 23, 2019
• Study Start: April 21, 2021
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: August 17, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)