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KHK2455 Alone and in Combination With Mogamulizumab in Subjects With Locally Advanced or Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT02867007
Recruitment Status : Completed
First Posted : August 15, 2016
Last Update Posted : August 10, 2021
Sponsor:
Information provided by (Responsible Party):
Kyowa Kirin, Inc.

Tracking Information
First Submitted Date  ICMJE August 4, 2016
First Posted Date  ICMJE August 15, 2016
Last Update Posted Date August 10, 2021
Study Start Date  ICMJE August 2016
Actual Primary Completion Date December 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 13, 2017)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 2 years ]
Safety assessment variables will include all adverse events (AEs) including serious and non-serious AEs, changes in clinical laboratory parameters, vital signs, 12-lead electrocardiograms, physical examination, and immunogenicity
Original Primary Outcome Measures  ICMJE
 (submitted: August 10, 2016)
  • Number of subjects reporting adverse events [ Time Frame: Screening through the first 56 days of treatment ]
  • Number of subjects reporting serious adverse events [ Time Frame: Screening through the first 56 days of treatment ]
  • Number of subjects experiencing dose-limiting toxicity [ Time Frame: Screening through the first 56 days of treatment ]
  • Percentage of subjects reporting adverse events [ Time Frame: Screening through the first 56 days of treatment ]
  • Percentage of subjects reporting serious adverse events [ Time Frame: Screening through the first 56 days of treatment ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE KHK2455 Alone and in Combination With Mogamulizumab in Subjects With Locally Advanced or Metastatic Solid Tumors
Official Title  ICMJE Multicenter, Open-label, Phase 1, Dose-escalation, Cohort-expansion, First-in-Human Study of KHK2455 Administered as Monotherapy and in Combination With Mogamulizumab in Adult Subjects With Locally Advanced or Metastatic Solid Tumors
Brief Summary The purpose of this study is to characterize the safety, tolerability, and determine the maximum tolerated dose (MTD) or the highest protocol-defined dose, in the absence of exceeding the MTD, of KHK2455 administered orally in combination with mogamulizumab to subjects with locally advanced or metastatic solid tumors.
Detailed Description

The study is designed as a 2-part, multicenter, open-label, Phase 1, dose-escalation, cohort-expansion study of KHK2455 as a monotherapy run-in (Cycle 0) followed by combination therapy with the anti-CCR4 antibody mogamulizumab (Cycle 1 and beyond).

Part 1 will identify the MTD or the highest protocol-defined dose, in the absence of exceeding the MTD, for the KHK2455 monotherapy run-in and for the combination regimen (KHK2455 monotherapy [Cycle 0] followed by KHK2455 + mogamulizumab combination [Cycle 1]). The dose escalation phase (Part 1) will enroll up to approximately 36 subjects.

Part 2, the cohort-expansion phase, will further explore the safety, tolerability, PK, PD, pharmacogenomics (PGx), and preliminary anti-tumor activity of KHK2455 administered as monotherapy and in combination with mogamulizumab in subjects with one cohort-specific tumor type. In Part 2, approximately 15 subjects with a selected tumor type will be enrolled and treated with the recommended KHK2455 dose established in Part 1 in combination with mogamulizumab.

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
  • Solid Tumor
  • Cancer
  • Carcinoma
Intervention  ICMJE
  • Drug: KHK2455
    oral dosing
  • Drug: Mogamulizumab
    i.v. administration
    Other Names:
    • Mogamulizumab: KW-0761
    • Poteligio
Study Arms  ICMJE Experimental: KHK2455 + Mogamulizumab

Part 1 (Dose Escalation Part): Will identify the MTD for the KHK2455 monotherapy run-in and for the combination regimen (KHK2455 monotherapy [Cycle 0] followed by KHK2455 +mogamulizumab combination [Cycle 1]).

Part 2 (Expansion Part): Subjects with a selected tumor type will be enrolled and treated with the recommended dose of KHK2455 established in Part 1 in combination with mogamulizumab.

Interventions:
  • Drug: KHK2455
  • Drug: Mogamulizumab
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 Completed
Actual Enrollment  ICMJE
 (submitted: February 23, 2021)
36
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2016)
50
Actual Study Completion Date  ICMJE December 15, 2019
Actual Primary Completion Date December 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject must have histological or cytological evidence of a solid malignancy
  • Subject must have measurable neoplastic disease according to the RECIST v1.1;
  • Subject must have locally advanced or metastatic solid tumor with no additional therapy options available that are known to provide clinical benefit per institutional standards;
  • Subject is able to understand and willing to sign the ICF, according to institutional standards, prior to the initiation of any study related procedures;
  • Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
  • Subject must have a life expectancy of > 3 months, in the Investigator's judgment;
  • Subject must have a left ventricular ejection fraction of ≥ 50%;
  • Subject must have adequate organ function as defined below. The following parameters must be evaluated within 28 days prior to Cycle 0 Day 1 (monotherapy run-in period):

    • Aspartate aminotransferase (AST) and/or ALT ≤ 2.5 × ULN
    • Total bilirubin ≤ 1.5 × ULN
    • Hemoglobin ≥ 9.6 g/dL
    • Serum creatinine ≤ 2.0 × ULN
    • Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
    • Absolute lymphocytes count ≥ 800 cells/mm3
    • Platelets ≥ 100 × 109/L
    • Albumin ≥ 2.0 g/dL
  • Subject has recovered (i.e., to Grade ≤ 1 or to a baseline level) from the effects of surgery, radiotherapy, chemotherapy, hormonal therapy, or other therapies for cancer; with the exception of vitiligo, alopecia, neuropathy, partial hearing loss, and/or endocrinopathies (for which no resolution is required);
  • Subject on prior chemotherapeutic, immunomodulator (such as anti-CTLA-4, anti-PD-1 or anti-PD-L1 inhibitor), investigational, or other therapies for the treatment of cancer must wait at least 28 days after the last dose of these therapies before administration of the first dose of the IMP.
  • Male subject and woman of child-bearing potential (WOCBP) must agree to use a medically-effective, double-barrier method of contraception (as defined in the ICF) to prevent pregnancy while on study and for 6 months after the last dose of IMP. WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months without an alternative medical cause). If the subject is a WOCBP, she must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Cycle 0 Day 1 (monotherapy run-in period; prior to receiving KHK2455);
  • Subject must have a brain scan performed during Screening or within 3 months prior to signing informed consent;
  • Subject must be able to swallow solid dosage forms.

Exclusion Criteria:

  • Subject is enrolled (concurrently) in another investigational study, with the exception of the follow-up period of another investigational study in which no anti-cancer therapy is being administered and where only data are being collected;
  • Subject who has been previously treated with an anti-CCR4 antibody or an IDO1 inhibitor;
  • Subject with a history of severe hypersensitivity reactions to any of the other excipients of the protocol IMPs (see Section 8.1.1);
  • Subject is a female who is pregnant or breast-feeding, or intends to become pregnant during their participation in the study (including up to 6 months after the last dose of IMP) or is a male who intends to father a child during their participation in the study (including up to 6 months after the last dose of IMP);
  • Subject has known primary immunodeficiency or active tuberculosis or tests positive for acquired human immunodeficiency virus;
  • Subject who tests positive for hepatitis B surface antigen (HBVsAg) or hepatitis C ribonucleic acid (RNA) indicating acute or chronic infection;
  • Subject who has undergone a major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of KHK2455 or is still recovering from prior surgery;
  • Subject has a mean QT interval corrected for heart rate using Bazett's (QTcB) or Fridericia's (QTcF) correction ≥ 500 ms calculated from 3 consecutive 12-lead ECGs at Screening;
  • Subject with an uncontrolled concurrent illness including, but not limited to, ongoing or active infection, significant hepatic disease (subjects with liver metastases who meet the inclusion criteria will be allowed ), pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial or other current severe lung disease including poorly controlled chronic obstructive pulmonary disease, malabsorption or protracted diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent;
  • Subjects with Gilbert's syndrome;
  • Subject with known active CNS metastasis, except primary brain tumors. Subjects with asymptomatic brain metastases or spinal cord compression who have been treated, are considered stable, and have not received steroid doses > 10 mg/day of prednisolone equivalent to treat these conditions prior to consent may be included;
  • Subject with any prior Grade ≥ 3 irAE to other therapeutic proteins or immunotherapy, and the reaction could not be controlled or prevented on subsequent infusion with standard therapies such as antihistamines, 5-hydroxytryptamine antagonists, or corticosteroids;
  • Subject with a history of organ transplant or allogeneic bone marrow transplant;
  • Subject currently using or have received immunosuppressive medications within 14 days prior to the first dose of KHK2455, with the exception of topical or systemic corticosteroids that are not to exceed 10 mg/day of prednisone or equivalent;
  • Subject with a history of autoimmune disease (e.g., ulcerative colitis, Crohn's disease, rheumatoid arthritis, Addison's syndrome, multiple sclerosis, uveitis, systemic lupus erythematosus or Wegener's granulomatosis). Subjects with vitiligo, endocrinopathies, and alopecia are allowed. Subjects with psoriasis not requiring systemic treatment within the past 6 months are allowed;
  • Subject who has a history of second primary cancer within the past 5 years, with the exception of:

    • Curatively resected non-melanoma skin cancer;
    • Curatively treated cervical intraepithelial neoplasia or prostate carcinoma with current prostate specific antigen < 0.01 ng/mL; or
    • Curatively treated ductal carcinoma in situ of the breast.
  • The subject has a condition(s) that, in the opinion of the Investigator and/or Sponsor, would interfere with evaluation of the IMP or interpretation of the subject's safety or study results.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02867007
Other Study ID Numbers  ICMJE 2455-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kyowa Kirin, Inc.
Study Sponsor  ICMJE Kyowa Kirin, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Kyowa Kirin, Inc.
Verification Date March 2020

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