Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 in Subjects With Metastatic or Locally 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: NCT04242147
Recruitment Status : Recruiting
First Posted : January 27, 2020
Last Update Posted : August 13, 2021
Sponsor:
Information provided by (Responsible Party):
Kadmon Corporation, LLC

Tracking Information
First Submitted Date  ICMJE January 23, 2020
First Posted Date  ICMJE January 27, 2020
Last Update Posted Date August 13, 2021
Actual Study Start Date  ICMJE June 3, 2020
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2020)
  • Occurrence of Dose Limiting Toxicities (DLTs) [ Time Frame: Up to week 5 of treatment ]
    To evaluate the number of subjects who experienced DLTs during the dose escalation phase
  • Treatment Emergent Adverse Events (TEAEs) and Related TEAEs by Severity [ Time Frame: Up to 90 days after last treatment ]
    To evaluate the number of TEAEs and related TEAEs by severity
  • Maximum Tolerated Dose (MTD) [ Time Frame: Through study completion, an average of 1 year ]
    To determine the safety/tolerability and the MTD of subjects during the dose escalation phase
  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Through study completion, an average of 1 year ]
    To determine the RP2D during the dose expansion phase
Original Primary Outcome Measures  ICMJE
 (submitted: January 23, 2020)
  • Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 90 days after last treatment ]
    To evaluate the treatment Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
  • Treatment Emergent Adverse Events (TEAEs) and Related TEAEs by Severity [ Time Frame: Up to 90 days after last treatment ]
    To evaluate the number of Treatment Emergent Adverse Events (TEAEs) and Related TEAEs by Severity
  • Dose Limiting Toxicities [ Time Frame: Up to Week 5 ]
    To evaluate the number of Subjects With Dose Limiting Toxicities (DLT)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2020)
  • Best Overall Response (BOR) [ Time Frame: Through study completion, an expected average of 1 year ]
    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
  • Duration Of Response (DOR) [ Time Frame: Through study completion, an expected average of 1 year ]
    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
  • Changes in immune correlates in peripheral blood [ Time Frame: Through study completion, an expected average of 1 year ]
    To evaluate changes in immune correlates of KD033 in peripheral blood to better understand the mechanism of action
  • Exploration of KD033 Pharmacokinetic (PK) Profile - Cmax [ Time Frame: Through study completion, an expected average of 1 year ]
    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)
  • Exploration of KD033 Pharmacokinetic (PK) Profile - AUC [ Time Frame: Through study completion, an expected average of 1 year ]
    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)
  • Exploration of Anti-KD033 Antibodies [ Time Frame: Through study completion, an expected average of 1 year ]
    To evaluate serum titers and assessment of neutralization of anti-KD033 antibodies using blood samples collected during the dose escalation and dose expansion phases
Original Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2020)
Objective response rate (ORR) of (NKTR) -214 [ Time Frame: Through study completion, an expected average of 1 year ]
To evaluate the objective response rate (ORR) of (NKTR)-214 based on investigator review of radiographic images
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KD033 in Subjects With Metastatic or Locally Advanced Solid Tumors.
Official Title  ICMJE 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.
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumor
Intervention  ICMJE Drug: KD033 for Injection
KD033 Monotherapy
Study Arms  ICMJE Experimental: Monotherapy
KD033 will be administered in sequential ascending doses as a monotherapy via intravenous (IV) administration every 2 weeks (Q2W)
Intervention: Drug: KD033 for Injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 23, 2020)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Miranda Ross (724)778-6170 miranda.ross@kadmon.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04242147
Other Study ID Numbers  ICMJE KD033-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kadmon Corporation, LLC
Study Sponsor  ICMJE Kadmon Corporation, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Kadmon Corporation, LLC
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP