Clinical Trials /

A Pharmacokinetic and Pharmacodynamic Study of DZ-002 in Patients With Advanced Solid Malignancies or Lymphoma

NCT04970992

Description:

The primary goal of this Phase 1 study is to characterize the safety and tolerability of DZ-002 and establish the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of DZ-002 administered on a weekly schedule in patients with solid tumors. Pharmacokinetics, pharmacodynamics, and the anti-tumor activity of DZ-002 will also be assessed.

Related Conditions:
  • Hodgkin Lymphoma
  • Malignant Solid Tumor
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Pharmacokinetic and Pharmacodynamic Study of DZ-002 in Patients With Advanced Solid Malignancies or Lymphoma
  • Official Title: A Pharmacokinetic and Pharmacodynamic Study of DZ-002 in Patients With Advanced Solid Malignancies or Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: DZ-002-101
  • NCT ID: NCT04970992

Conditions

  • Solid Tumor
  • Lymphoma

Interventions

DrugSynonymsArms
DZ-002Dose escalation and cohort expansion Q1W

Purpose

The primary goal of this Phase 1 study is to characterize the safety and tolerability of DZ-002 and establish the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of DZ-002 administered on a weekly schedule in patients with solid tumors. Pharmacokinetics, pharmacodynamics, and the anti-tumor activity of DZ-002 will also be assessed.

Detailed Description

      This is a single center, first-in-human, Phase 1, safety, PK and pharmacodynamic study of
      DZ-002 in patients with solid tumors who have failed standard therapies. The study will be
      conducted in 2 phases, a dose escalation phase and a dose expansion phase. The
      dose-escalation phase will first determine the MTD and/or RP2D of DZ-002 in patients with
      advanced cancers. Subsequently, the MTD and/or RP2D will be investigated in 2 expansion
      treatment groups of castration-resistant prostate cancer (CRPC) and advanced pancreatic
      cancer. Patients who are determined to be eligible, based on Screening assessments, will be
      enrolled in the study and will receive their first dose of study therapy on Cycle 1 Day 1.
      All patients will receive DZ-102 administered as a weekly intravenous (IV) infusion on days
      1, 8, 15, and 22 of a 28-day cycle. The dose of DZ-002 will be dependent on the cohort in
      which the patient is enrolled.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalation and cohort expansion Q1WExperimentalDZ-002 treatment once every week
  • DZ-002

Eligibility Criteria

        Inclusion Criteria:

          1. Histopathologically confirmed diagnosis of an advanced, unresectable, or metastatic
             solid malignant tumor (including lymphoma; dose-escalation phase only) that has failed
             to respond to standard therapies;

          2. Male or female patients age 18 or older;

          3. Measurable or evaluable disease by RECIST v 1.1, or PCWG3 for prostate cancer;

          4. Capable of understanding and complying with protocol requirements;

          5. A life expectancy of greater than 8 weeks at Screening;

          6. An ECOG PS of 0 to 2;

          7. Written informed consent from the patient or the patient's legally acceptable
             representative prior to the initiation of any study procedures;

          8. Adequate bone marrow, liver, and renal function as defined below:

               -  Hemoglobin ≥ 8.0 g/dL (transfusions and/or erythropoietic stimulating growth
                  factors allowed);

               -  Absolute neutrophil count ≥ 1500/μL;

               -  Platelet count ≥ 75,000/ μL;;

               -  Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × the upper limit
                  of normal (ULN) or ≤ 5 × ULN for patients with known hepatic metastases;

               -  Total serum bilirubin ≤ 1.5× ULN or ≤ 2 .0 × ULN if liver metastases are present.
                  Patients with a known history of Gilbert's syndrome (≤ 3.0 × ULN) and/or isolated
                  elevations of indirect bilirubin are eligible for study participation;

               -  Estimated creatinine clearance ≥ 40 mL/min(using the Cockcroft Gault formula);

          9. Adequate cardiac function as estimated by left ventricular ejection fraction (LVEF) >
             50% by multiple-gated acquisition (MUGA) or echocardiogram (ECHO);

         10. Negative pregnancy test for women of childbearing potential (women of childbearing
             potential and men must agree to use adequate contraception [hormonal or barrier method
             of birth control] prior to study entry and for the duration of study participation.

        [NOTE: Sexual abstinence is considered a highly effective method only if defined as
        refraining from heterosexual intercourse during the entire period of risk associated with
        the study intervention. The reliability of sexual abstinence needs to be evaluated in
        relation to the duration of the study and the preferred and usual lifestyle of the
        patient]. Should a woman become pregnant or suspect she is pregnant while participating in
        this study, she should inform her treating physician immediately).

        Exclusion Criteria:

          1. New York Heart Association (see Appendix 5) Class III or IV cardiac disease,
             myocardial infarction within the past 6 months, unstable arrhythmia, a history of risk
             factors for Torsades de Pointes, including heart failure, hypokalemia, and family
             history of long QTc syndrome, or evidence of ischemia on ECG;

          2. Baseline QTc exceeding 470 msec (using the Fridericia's formula) and/or patients
             receiving Class 1A or Class III antiarrhythmic agents or concomitant medications that
             prolong the QT/QTc interval;

          3. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic
             therapy;

          4. Treatment with simvastatin unless it can be stopped prior to and during the study.

          5. Treatment with strong inhibitors and inducers of CYP3A4 or narrow therapeutic index
             substrates of CY3A4, CYP2B6, CYP1A2, CYP2C9 and CYP2C8, unless these can be stopped
             prior to and during the study

          6. Known sensitivity to DZ-002 or drug excipients

          7. Pregnant (confirmed by serum or urine pregnancy test) or is breast feeding;

          8. Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy
             within 30 days prior to study entry (6 weeks for nitrosoureas or Mitomycin C);

          9. Unwillingness or inability to comply with procedures required in this protocol;

         10. Known infection with human immunodeficiency virus and CD4 lymphocyte count < 200
             cells/mm3 , or active hepatitis B virus, or hepatitis C virus infections;

         11. Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other
             conditions) that could compromise protocol objectives in the opinion of the
             investigator and/or the Sponsor;

         12. Patients who are currently receiving any other investigational agent.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of treatment emergent adverse events (TEAEs)
Time Frame:24 months
Safety Issue:
Description:Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit

Secondary Outcome Measures

Measure:Tumor response
Time Frame:24 months
Safety Issue:
Description:Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and the Prostate Cancer Working Group 3 (PCWG3) for prostate cancer
Measure:AUC
Time Frame:56 days
Safety Issue:
Description:Area Under the Plasma Concentration versus Time Curve of DZ-002
Measure:Cmax
Time Frame:56 days
Safety Issue:
Description:Maximum Plasma Concentration of DZ-002
Measure:Tmax
Time Frame:56 days
Safety Issue:
Description:Time to reach maximum (peak) plasma concentration of
Measure:t1/2
Time Frame:56 days
Safety Issue:
Description:Terminal half-life of DZ-002
Measure:Clearance
Time Frame:56 days
Safety Issue:
Description:Total body clearance of the drug from plasma (CL) of DZ-002
Measure:Volume of distribution
Time Frame:56 days
Safety Issue:
Description:Apparent volume of distribution of DZ-002

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Da Zen Theranostics Inc

Last Updated

August 12, 2021