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

NCT02867007 | Completed Phase 1

• 1 other identifier: 2455-001
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 4

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.

Conditions

Solid Tumor; Cancer; Carcinoma

Keywords

KW-0761; KHK2455; Metastatic Solid Tumors; Locally Advanced Solid Tumors; Mogamulizumab; Oncology; Anti-Tumor

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  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

  Up to 2 years

Study Arms (1)

KHK2455 + Mogamulizumab

EXPERIMENTAL

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.

Drug: KHK2455; Drug: Mogamulizumab

Interventions

KHK2455 DRUG

oral dosing

KHK2455 + Mogamulizumab

Mogamulizumab DRUG

i.v. administration

Also known as: Mogamulizumab: KW-0761, Poteligio

KHK2455 + Mogamulizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;
• 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:

Sponsors & Collaborators

• Kyowa Kirin, Inc.: lead

Study Sites (4)

Unknown Facility

Tampa, Florida, 33612, United States

Location

Unknown Facility

Albuquerque, New Mexico, 87106, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Paris, Villejuif, 94800, France

Location

Related Publications (1)

• Yap TA, Rixe O, Baldini C, Brown-Glaberman U, Efuni S, Hong DS, Massard C, Muzaffar J, Varga A, Yilmaz E, Ikawa Y, Shiue LH, Liu Y, Hruska MW, Zhao H, Tokunaga A, Sahebjam S. First-in-human phase 1 study of KHK2455 monotherapy and in combination with mogamulizumab in patients with advanced solid tumors. Cancer. 2025 Jul 1;131(13):e35939. doi: 10.1002/cncr.35939.

  PMID: 40536766 DERIVED

MeSH Terms

Conditions

Neoplasms; Carcinoma

Interventions

mogamulizumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 15, 2016
• Study Start: August 1, 2016
• Primary Completion: December 15, 2019
• Study Completion: December 15, 2019
• Last Updated: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); US (3)