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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05118841
Recruitment Status : Recruiting
First Posted : November 12, 2021
Last Update Posted : February 2, 2022
Sponsor:
Information provided by (Responsible Party):
Nanjing Zenshine Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: ZX-4081 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, First in Human, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZX-4081 in Patients With Advanced Solid Tumors
Actual Study Start Date : January 3, 2022
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2024

Arm Intervention/treatment
Experimental: ZX-4081 Dose Level 1
Starting dose (SD) of ZX-4081 administered orally twice daily (BID) in a 28-day cycle
Drug: ZX-4081
Twice daily (BID), oral dosing of ZX-4081 at the assigned dose level in a 28-day cycle

Experimental: ZX-4081 Dose Level 2
2-times the SD of ZX-4081 administered orally BID in a 28-day cycle
Drug: ZX-4081
Twice daily (BID), oral dosing of ZX-4081 at the assigned dose level in a 28-day cycle

Experimental: ZX-4081 Dose Level 3
4-times the SD of ZX-4081 administered orally BID in a 28-day cycle
Drug: ZX-4081
Twice daily (BID), oral dosing of ZX-4081 at the assigned dose level in a 28-day cycle

Experimental: ZX-4081 Dose Level 4
6-times the SD of ZX-4081 administered orally BID in a 28-day cycle
Drug: ZX-4081
Twice daily (BID), oral dosing of ZX-4081 at the assigned dose level in a 28-day cycle

Experimental: ZX-4081 Dose Level 5
8-times the SD of ZX-4081 administered orally BID in a 28-day cycle
Drug: ZX-4081
Twice daily (BID), oral dosing of ZX-4081 at the assigned dose level in a 28-day cycle

Experimental: ZX-4081 Dose Level 6
10-times the SD of ZX-4081 administered orally BID in a 28-day cycle
Drug: ZX-4081
Twice daily (BID), oral dosing of ZX-4081 at the assigned dose level in a 28-day cycle

Experimental: ZX-4081 Expansion Dose Level
Recommended Phase 2 Dose (RP2D) (to be determined) of ZX-4081 administered orally BID in a 28-day cycle
Drug: ZX-4081
Twice daily (BID), oral dosing of ZX-4081 at the assigned dose level in a 28-day cycle




Primary Outcome Measures :
  1. Determine the recommended Phase 2 dose (RP2D) of ZX-4081 [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    To assess number of patients experiencing dose-limiting toxicities (DLTs) in the dose escalation phase

  2. Safety and tolerability of ZX-4081 [ Time Frame: From first dose of ZX-4081 through 28 days after the last ZX-4081 treatment (up to 2 years); each cycle is 28 days ]
    To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-4081 in the dose escalation and dose expansion phases


Secondary Outcome Measures :
  1. Peak Plasma Concentration of ZX-4081 [ Time Frame: Days 1, 8, and 15 of Cycle 1 (each cycle is 28 days) ]
    To evaluate the maximum observed concentration (Cmax) after single and repeated oral, twice daily (BID) doses of ZX-4081

  2. Area under the plasma concentration of ZX-4081 [ Time Frame: Days 1, 8, and 15 of Cycle 1 (each cycle is 28 days) ]
    To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, BID doses of ZX-4081

  3. Half-life of ZX-4081 [ Time Frame: Days 1, 8, and 15 of Cycle 1 (each cycle is 28 days) ]
    To evaluate the half-life of ZX-4081 after single and repeated oral, BID doses of ZX-4081

  4. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    To evaluate the objective response rate (ORR) as determined by the specific disease response criteria

  5. Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    To examine the duration of response (DoR), defined as time from the date of first documentation of response to the date of the first documentation of progressive disease (PD), or death due to any cause

  6. Progression Free Survival (PFS) [ Time Frame: Up to 2 years ]
    To examine the the progression free survival (PFS), defined as time from the date of first dose of study treatment to the first date of documentation of PD, or death due to any cause

  7. Overall Survival (OS) [ Time Frame: Up to 2 years ]
    To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause

  8. Peripheral myeloid-derived suppressor cell (MDSC) proportion in the blood [ Time Frame: Cycle 1 Day1 , Cycle 2 Day 1, and Cycle 3 Day 1 (each cycle is 28 days) ]
    To assess the changes of peripheral MDSC proportion in the blood after single and repeated oral, BID doses of ZX-4081

  9. T cell composition and activation status [ Time Frame: Cycle 1 Day1 , Cycle 2 Day 1, and Cycle 3 Day 1 (each cycle is 28 days) ]
    To assess the impact on T cell profiles after repeated oral, BID doses of ZX-4081



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Measurable disease with at least 1 lesion amenable to response assessment per RECIST 1.1.
  3. Demonstrate adequate organ function. All screening laboratories should be performed within 14 days of treatment initiation.
  4. Has a performance status of 0-2 on the ECOG Performance Scale.
  5. Life expectancy >12 weeks at baseline.
  6. 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.

  7. 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.
  8. Age ≥18 years at screening.
  9. Able and willing to provide written informed consent and to follow study instructions.

Exclusion Criteria:

  1. Patient has disease that is suitable for therapy administered with curative intent.
  2. Untreated or uncontrolled central nervous system (CNS) involvement.
  3. 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.
  4. 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.
  5. Systemic corticosteroids at doses exceeding 10 mg/day prednisone or equivalent.
  6. Patient has an active infection requiring systemic therapy.
  7. 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.
  8. Patients with unstable/inadequate cardiac function:

    1. New York Heart Association Class 3 or 4 congestive heart failure,
    2. Uncontrolled hypertension,
    3. Acute coronary syndrome within 6 months,
    4. Clinical important cardiac arrhythmia,
    5. 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.
  9. A history of additional risk factors for Torsades de Pointes(TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
  10. The use of concomitant medications that prolong the QT/QTc interval.
  11. Concomitant use or recent use (at least 2 weeks before the start of ZX-4081 treatment) of drugs that are known to be strong CYP3A4/5 inhibitors and CYP3A4/5 inducers (See 5.4.2 for a list of study medications not allowed during this study).
  12. Concomitant use of drugs that are sensitive substrates with narrow therapeutic index for one of the following: CYP2C9, CYP2C19, CYP2C8, CYP2D6 and CYP3A4 (See 5.4.2 for a list of study medications not allowed during this study).
  13. Concomitant use of drugs that are sensitive substrates with narrow therapeutic index for one of the following transporters: P-glycoprotein (P-gp) and Breast Cancer resistance Protein (BCRP).
  14. Recent use a proton pump inhibitor (within 4 days prior to the start ZX-4081 treatment) or a histamine H2 blocker (within 2 days prior to the start of ZX-4081 treatment).
  15. Uncontrolled concurrent illness.
  16. Patient has concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer who has undergone potentially curative therapy with no evidence of disease. Patients with other previous malignancies are eligible if disease-free for >2 years.
  17. Participation in another clinical trial of an investigational agent within 30 days of screening.
  18. Patient has known psychiatric, substance abuse or other disorders that would interfere with cooperation with the requirements of the trial, in the opinion of the investigator.
  19. Patients who are pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 30 days after the last dose of trial treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05118841


Contacts
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Contact: Xiaoli Qin, PhD (+1) 650-799-2796 xiaoli.qin@zenshine-pharma.com
Contact: Edgar Bautista (+1) 310-867-9063 Edgar@zenshine-pharma.com

Locations
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United States, North Carolina
Carolina BioOncology Recruiting
Huntersville, North Carolina, United States, 28078
Contact: John Powderly, MD         
Sponsors and Collaborators
Nanjing Zenshine Pharmaceuticals
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Responsible Party: Nanjing Zenshine Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05118841    
Other Study ID Numbers: ZX-4081
First Posted: November 12, 2021    Key Record Dates
Last Update Posted: February 2, 2022
Last Verified: January 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms