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A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 in Subjects With Metastatic or Locally Advanced Solid Tumors.

NCT04242147

Description:

This is a First-in-Human, open-label, sequential dose-escalation and dose-expansion study of KD033 in adult subjects with advanced or metastatic solid tumors. The main purpose of this study is to test KD033 at different dose levels to see if it is safe and well tolerated when given once every 2 weeks. Additional purposes of the study are to find out whether the study drug has anti-cancer effects and how the study drug is processed by the body.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 in Subjects With Metastatic or Locally Advanced Solid Tumors.
  • Official Title: A Phase 1, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 in Subjects With Metastatic or Locally Advanced Solid Tumors.

Clinical Trial IDs

  • ORG STUDY ID: KD033-101
  • NCT ID: NCT04242147

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
KD033 for InjectionMonotherapy

Purpose

This is a First-in-Human, open-label, sequential dose-escalation and dose-expansion study of KD033 in adult subjects with advanced or metastatic solid tumors. The main purpose of this study is to test KD033 at different dose levels to see if it is safe and well tolerated when given once every 2 weeks. Additional purposes of the study are to find out whether the study drug has anti-cancer effects and how the study drug is processed by the body.

Detailed Description

      During the dose escalation phase of the study, cohorts of 3 to 6 subjects with metastatic or
      locally advanced solid tumors will receive KD033 at escalating dose levels. Upon completion
      of the dose escalation part of the study, at least 15 subjects will be enrolled in the
      expansion cohort to further confirm the recommended phase 2 dose.
    

Trial Arms

NameTypeDescriptionInterventions
MonotherapyExperimentalKD033 will be administered in sequential ascending doses as a monotherapy via intravenous (IV) administration every 2 weeks (Q2W)
  • KD033 for Injection

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed/documented advanced and/or metastatic solid
             tumor with at least one tumor lesion of location accessible to biopsy per clinical
             judgement of treating physician.

          2. Measurable disease per RECIST v1.1 guidelines.

          3. Life expectancy of at least 3 months.

          4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ≤ 1.

          5. Adequate organ and bone marrow functions.

          6. All toxicities related to prior radiotherapy, chemotherapy, or surgical procedure must
             have recovered to baseline or Grade ≤ 1 based on NCI-CTCAE v5.0 except alopecia (any
             grade), Grade 2 peripheral neuropathy and adverse events that are clinically non
             significant or stable on supportive care.

          7. All subjects, male and female, who are not surgically sterilized or postmenopausal
             must agree to use "highly effective methods of contraception" during the study and for
             at least 60 days after the last dose of KD033.

        Exclusion Criteria:

          1. Use of immunotherapy, biological therapy, cytokine therapy < 21 days prior to the
             first dose of study drug.

          2. Use of immunomodulating agents < 21 days prior to the first dose of study drug.

          3. Use of chemotherapy and approved tyrosine kinase inhibitor (TKI) therapy < 14 days
             prior to the first dose of study drug.

          4. Anti PD-L1 or anti PD-1 therapy < 6 weeks prior to the first dose of study drug.

          5. Ongoing or recent (within 2 years) evidence of significant autoimmune disease that
             required systemic immunosuppressive treatments.

          6. Systemic therapy with immunosuppressive agents including corticosteroids within 14
             days before the start of trial treatment.

          7. Rapidly progressive disease which, in the opinion of Investigator, may predispose to
             inability to tolerate treatment or trial procedure.

          8. History or clinical evidence of central nervous system primary tumors or metastases
             including leptomeningeal metastases unless they have been previously treated,
             demonstrated no progression at least 1 months, are asymptomatic and have had no
             requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before
             Screening - Subjects with suspected brain metastases at Screening should undergo a
             CT/MRI of the brain prior to study entry.

          9. Receipt of any organ transplantation including hematopoietic cell transplantation.

         10. Has a paraneoplastic syndrome of autoimmune nature.

         11. History of interstitial lung disease or severe obstructive pulmonary disease.

         12. Clinically significant cardiovascular/cerebrovascular disease.

         13. QTc(F) interval > 450 ms for men or > 470 ms for women)

         14. Left ventricular ejection fraction (LVEF) < 50% as measured by an echocardiogram
             (ECHO).

         15. Active infection requiring therapy.

        Other protocol-defined exclusion criteria could apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of Dose Limiting Toxicities (DLTs)
Time Frame:Up to week 5 of treatment
Safety Issue:
Description:To evaluate the number of subjects who experienced DLTs during the dose escalation phase

Secondary Outcome Measures

Measure:Best Overall Response (BOR)
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:To evaluate the best overall response from study treatment according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria per Investigator assessment
Measure:Duration Of Response (DOR)
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:To evaluate the duration of response from study treatment according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria per Investigator assessment
Measure:Changes in immune correlates in peripheral blood
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:To evaluate changes in immune correlates of KD033 in peripheral blood to better understand the mechanism of action
Measure:Exploration of KD033 Pharmacokinetic (PK) Profile - Cmax
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:The PK profile of KD033 will be evaluated using blood samples collected during the dose escalation and dose expansion phases to determine the maximum concentration (Cmax)
Measure:Exploration of KD033 Pharmacokinetic (PK) Profile - AUC
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:The PK profile of KD033 will be evaluated using blood samples collected during the dose escalation and dose expansion phases to determine area under the curve (AUC)
Measure:Exploration of Anti-KD033 Antibodies
Time Frame:Through study completion, an expected average of 1 year
Safety Issue:
Description:To evaluate serum titers and assessment of neutralization of anti-KD033 antibodies using blood samples collected during the dose escalation and dose expansion phases

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kadmon Corporation, LLC

Last Updated

February 5, 2021