Dose-Escalation and Dose-Expansion Study of ZX-4081 in Patients With Advanced Solid Tumors

NCT05118841 | Unknown Phase 1 FDA Drug

• 1 other identifier: ZX-4081
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1, first-in-human, open-label, multicenter, dose escalation and dose expansion study to investigate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of ZX-4081 administered orally (PO) twice daily (BID) in 28-day cycles in patients with Advanced Solid Tumors.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Determine the recommended Phase 2 dose (RP2D) of ZX-4081

  To assess number of patients experiencing dose-limiting toxicities (DLTs) in the dose escalation phase

  At the end of Cycle 1 (each cycle is 28 days)

• Safety and tolerability of ZX-4081

  To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-4081 in the dose escalation and dose expansion phases

  From first dose of ZX-4081 through 28 days after the last ZX-4081 treatment (up to 2 years); each cycle is 28 days

Secondary Outcomes (9)

• Peak Plasma Concentration of ZX-4081

  Days 1, 8, and 15 of Cycle 1 (each cycle is 28 days)

• Area under the plasma concentration of ZX-4081

  Days 1, 8, and 15 of Cycle 1 (each cycle is 28 days)

• Half-life of ZX-4081

  Days 1, 8, and 15 of Cycle 1 (each cycle is 28 days)

• Objective response rate (ORR)

  Up to 2 years

• Duration of Response (DOR)

  Up to 2 years

Study Arms (7)

ZX-4081 Dose Level 1

EXPERIMENTAL

Starting dose (SD) of ZX-4081 administered orally twice daily (BID) in a 28-day cycle

Drug: ZX-4081

ZX-4081 Dose Level 2

EXPERIMENTAL

2-times the SD of ZX-4081 administered orally BID in a 28-day cycle

Drug: ZX-4081

ZX-4081 Dose Level 3

EXPERIMENTAL

4-times the SD of ZX-4081 administered orally BID in a 28-day cycle

Drug: ZX-4081

ZX-4081 Dose Level 4

EXPERIMENTAL

6-times the SD of ZX-4081 administered orally BID in a 28-day cycle

Drug: ZX-4081

ZX-4081 Dose Level 5

EXPERIMENTAL

8-times the SD of ZX-4081 administered orally BID in a 28-day cycle

Drug: ZX-4081

ZX-4081 Dose Level 6

EXPERIMENTAL

10-times the SD of ZX-4081 administered orally BID in a 28-day cycle

Drug: ZX-4081

ZX-4081 Expansion Dose Level

EXPERIMENTAL

Recommended Phase 2 Dose (RP2D) (to be determined) of ZX-4081 administered orally BID in a 28-day cycle

Drug: ZX-4081

Interventions

ZX-4081 DRUG

Twice daily (BID), oral dosing of ZX-4081 at the assigned dose level in a 28-day cycle

ZX-4081 Dose Level 1; ZX-4081 Dose Level 2; ZX-4081 Dose Level 3; ZX-4081 Dose Level 4; ZX-4081 Dose Level 5; ZX-4081 Dose Level 6; ZX-4081 Expansion Dose Level

Eligibility Criteria

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

You may qualify if:

• Metastatic or locally advanced solid tumor malignancies (breast cancer, urothelial cancer, ovarian cancer, melanoma, NSCLC, renal cell carcinoma, squamous cell cancer of the head and neck, colorectal cancer, and hepatocellular carcinoma) that has progressed on, is refractory to, intolerant to, or for which there is no curative standard of care therapy.
• Measurable disease with at least 1 lesion amenable to response assessment per RECIST 1.1.
• Demonstrate adequate organ function. All screening laboratories should be performed within 14 days of treatment initiation.
• Has a performance status of 0-2 on the ECOG Performance Scale.
• Life expectancy \>12 weeks at baseline.
• Women of childbearing potential must have negative serum or urine pregnancy test within 72 hours prior to receiving the first study drug administration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Women of childbearing potential must be willing to use an adequate method of contraception from 30 days prior to the first study drug administration and 120 days following last day study drug administration.
• Male patients of childbearing potential must be surgically sterile, or must agree to use adequate method of contraception during the study and at least 120 days following the last day of study drug administration.
• Age ≥18 years at screening.
• Able and willing to provide written informed consent and to follow study instructions.

You may not qualify if:

• Patient has disease that is suitable for therapy administered with curative intent.
• Untreated or uncontrolled central nervous system (CNS) involvement.
• Any concurrent or recent use (within 28 days or 5 half-lives, whichever is longer) of chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
• Unresolved toxicities from prior therapy, defined as having not resolved to NCI CTCAE v5.0 Grade 0 or 1, with exception of alopecia and vitiligo.
• Systemic corticosteroids at doses exceeding 10 mg/day prednisone or equivalent.
• Patient has an active infection requiring systemic therapy.
• Patients who have known active HIV, Hepatitis or active COVID-19 infection. (Patients who have been vaccinated against Hepatitis B and who are positive only for the Hepatitis B surface antibody are permitted to participate in the study). Patients who are positive for hepatitis B or C virus must be tested for and have an undetectable viral load.
• Patients with unstable/inadequate cardiac function:
• New York Heart Association Class 3 or 4 congestive heart failure,
• Uncontrolled hypertension,
• Acute coronary syndrome within 6 months,
• Clinical important cardiac arrhythmia,
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>470 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction formula.
• A history of additional risk factors for Torsades de Pointes(TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• The use of concomitant medications that prolong the QT/QTc interval.

Sponsors & Collaborators

• Nanjing Zenshine Pharmaceuticals: lead

Study Sites (1)

Carolina BioOncology

Huntersville, North Carolina, 28078, United States

RECRUITING

Central Study Contacts

Xiaoli Qin, PhD

CONTACT

(+1) 650-799-2796; xiaoli.qin@zenshine-pharma.com

Edgar Bautista

CONTACT

(+1) 310-867-9063; Edgar@zenshine-pharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: November 12, 2021
• Study Start: January 3, 2022
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2024
• Last Updated: February 2, 2022

Record last verified: 2022-01

Locations

US (1)