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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.

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 : July 7, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Kadmon, a Sanofi Company )

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 and when given weekly. 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, bi-weekly and weekly dosing cohorts of 3 to 6 subjects with metastatic or locally advanced solid tumors will receive KD033 at escalating dose levels. Each cohort will consist of a minimum of 3 subjects to be treated with KD033 at each dose level. Expansion to 6 subjects per cohort will occur if 1 of 3 subjects experiences a DLT while also allowing for a +1 subject enrollment overfill.

The study plans for up to 7 dose escalation cohorts on a bi-weekly dosing regimen and up to 5 dose escalation cohorts on a weekly dosing regimen. Weekly dosing escalation cohorts will enroll in parallel to the bi-weekly dosing escalation cohorts.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
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 : August 8, 2023
Estimated Study Completion Date : August 8, 2023

Arm Intervention/treatment
Experimental: Bi-weekly Monotherapy Dosing Regimen
For the biweekly dose escalation cohorts, 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

Experimental: Weekly Monotherapy Dosing Regimen
For the weekly dose escalation cohorts, KD033 will be administered in sequential ascending doses as a monotherapy via intravenous (IV) administration once a week (QW).
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

  7. Exploration of PFS and OS [ Time Frame: Through study completion, an expected average of 1 year ]
    To assess the progression-free survival (PFS) and overall survival (OS) of all treated patients

  8. Exploration of immune correlates/other biomarkers of KD033 in blood and tumor. [ Time Frame: Through study completion, an expected average of 1 year ]
    To evaluate the immune correlates and/or other biomarkers of KD033 blood and tumor



Information from the National Library of Medicine

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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. 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.
  8. Women of childbearing potential must have a negative pregnancy test within 7 days prior to KD033 treatment.
  9. Ability to understand the purpose of the study, provide signed and dated informed consent from the subject/legal representative prior to performing any protocol-related procedures and able to comply with the study procedures and any locally required authorization.
  10. Subjects must be willing to provide a tumor biopsy at the following time points: Pre-treatment and at Cycle 4, Day 1. All other study eligibility criteria must be met before any biopsy sample is obtained.

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. Radiotherapy within 14 days before the start of trial treatment (prior diagnostic biopsy is permitted), with the exception of palliative radiation as described: patients assigned to radiotherapy require at least 1 additional lesion that can be safely irradiated while sparing the index lesion(s), and for which radiation at the limited, palliative doses contemplated would be considered medically appropriate; The lesion should be causing some signs or symptoms (e.g., tumor-related pain), for which radiation is indicated per the physician's standard clinical practice.
  6. Use of any investigational drug or have major surgery within 28 days before the start of trial treatment
  7. Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required systemic immunosuppressive treatments.
  8. Systemic therapy with immunosuppressive agents including corticosteroids within 14 days before the start of trial treatment.
  9. Rapidly progressive disease which, in the opinion of Investigator, may predispose to inability to tolerate treatment or trial procedure.
  10. 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.
  11. Receipt of any organ transplantation including hematopoietic cell transplantation.
  12. Has a paraneoplastic syndrome of autoimmune nature.
  13. History of interstitial lung disease or severe obstructive pulmonary disease.
  14. Clinically significant cardiovascular/cerebrovascular disease.
  15. QTc(F) interval > 450 ms for men or > 470 ms for women)
  16. Left ventricular ejection fraction (LVEF) < 50% as measured by an echocardiogram (ECHO).
  17. Active infection requiring therapy.
  18. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding.
  19. Pregnant or breast-feeding women
  20. Known severe hypersensitivity reactions to monoclonal antibodies, any history of or recent (within 6 months) of anaphylaxis
  21. Vaccine administration within 4 weeks of investigational drug administration. Vaccination with live vaccines while on trial is prohibited. Administration of inactivated vaccines like inactivated influenza vaccines is allowed. COVID-19 vaccines are approved to be administered prior to KD033 administration and during the treatment phase,; however, it is preferred to not vaccinate during the 28-day DLT period.

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
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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United States, California
UCLA Hematology/Oncology, 2020 Santa Monica Boulevard, Suite 600 - Site 042 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 - 665 Elm St - Site 062 Recruiting
Buffalo, New York, United States, 14263
Contact: John Pineda    716-845-1300 ext 5054    John.Pineda@RoswellPark.org   
Principal Investigator: Christos Fountzilas, MD         
United States, Pennsylvania
Fox Chase Cancer Center - 333 Cottman Avenue - Site 141 Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Dana Haagen, BA, BS    215-214-3908    Dana.Haagen@fccc.edu   
Principal Investigator: Anthony Olszanski, MD         
University of Pittsburgh Medical Center - Hillman Cancer Center - 5150 Centre Avenue, Suite 301 - Site 132 Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Sarah Behr    412-623-6028    IDDCReferrals@upmc.edu   
Principal Investigator: Jason Luke, MD, FACP         
Sponsors and Collaborators
Kadmon, a Sanofi Company
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Responsible Party: Kadmon, a Sanofi Company
ClinicalTrials.gov Identifier: NCT04242147    
Other Study ID Numbers: TED17644
KD033-101 ( Other Identifier: Kadmon )
First Posted: January 27, 2020    Key Record Dates
Last Update Posted: July 7, 2022
Last Verified: July 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