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
Overview
- Phase
- Phase 1
- Intervention
- KHK2455
- Conditions
- Solid Tumor
- Sponsor
- Kyowa Kirin, Inc.
- Enrollment
- 36
- Primary Endpoint
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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;
Arms & Interventions
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.
Intervention: KHK2455
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.
Intervention: Mogamulizumab
Outcomes
Primary Outcomes
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