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 : June 1, 2021
Sponsor:
Information provided by (Responsible Party):
Kadmon Corporation, LLC

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: KD033 for Injection Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : June 3, 2020
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : March 2023

Arm Intervention/treatment
Experimental: Monotherapy
KD033 will be administered in sequential ascending doses as a monotherapy via intravenous (IV) administration every 2 weeks (Q2W)
Drug: KD033 for Injection
KD033 Monotherapy




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Recommended Phase 2 Dose (RP2D) [ Time Frame: Through study completion, an average of 1 year ]
    To determine the RP2D during the dose expansion phase


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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)

  5. 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)

  6. 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



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


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): NCT04242147


Contacts
Layout table for location contacts
Contact: Miranda Schlitt (724)778-6170 miranda.schlitt@kadmon.com

Locations
Layout table for location information
United States, California
UCLA Hematology/Oncology, Santa Monica Recruiting
Santa Monica, California, United States, 90404
Contact: Christopher Lim    310-633-8400 ext 16043    christopherlim@mednet.ucla.edu   
Principal Investigator: Lee S Rosen, MD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Cayla Ford    716-845-2300 ext 4924    cayla.ford@roswellpark.org   
Principal Investigator: Igor Puzanov, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Kelsie Peta, BSN, RN    215-728-2175    Kelsie.peta@fccc.edu   
Principal Investigator: Anthony Olszanski, MD         
University of Pittsburgh Medical Center - Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Krystle Eaton, BSN    412-623-4511    mientkiewiczk@upmc.edu   
Principal Investigator: Jason Luke, MD, FACP         
Sponsors and Collaborators
Kadmon Corporation, LLC
Layout table for additonal information
Responsible Party: Kadmon Corporation, LLC
ClinicalTrials.gov Identifier: NCT04242147    
Other Study ID Numbers: KD033-101
First Posted: January 27, 2020    Key Record Dates
Last Update Posted: June 1, 2021
Last Verified: May 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms