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

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 additionaltherapy options available that are known to provide clinical benefit per institutionalstandards;
• Subject is able to understand and willing to sign the ICF, according to institutionalstandards, prior to the initiation of any study related procedures;
• Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0or 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 parametersmust 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 ofsurgery, radiotherapy, chemotherapy, hormonal therapy, or other therapies for cancer;with the exception of vitiligo, alopecia, neuropathy, partial hearing loss, and/orendocrinopathies (for which no resolution is required);
• Subject on prior chemotherapeutic, immunomodulator (such as anti-CTLA-4, anti-PD-1 oranti-PD-L1 inhibitor), investigational, or other therapies for the treatment of cancermust wait at least 28 days after the last dose of these therapies beforeadministration of the first dose of the IMP.
• Male subject and woman of child-bearing potential (WOCBP) must agree to use amedically-effective, double-barrier method of contraception (as defined in the ICF) toprevent pregnancy while on study and for 6 months after the last dose of IMP. WOCBPincludes any female who has experienced menarche and who has not undergone successfulsurgical sterilization or is not postmenopausal (defined as amenorrhea ≥ 12consecutive 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 urinepregnancy test on Cycle 0 Day 1 (monotherapy run-in period; prior to receivingKHK2455);
• Subject must have a brain scan performed during Screening or within 3 months prior tosigning informed consent;
• Subject must be able to swallow solid dosage forms.

Exclusion Criteria:

• Subject is enrolled (concurrently) in another investigational study, with theexception of the follow-up period of another investigational study in which noanti-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 IDO1inhibitor;
• Subject with a history of severe hypersensitivity reactions to any of the otherexcipients of the protocol IMPs (see Section 8.1.1);
• Subject is a female who is pregnant or breast-feeding, or intends to become pregnantduring their participation in the study (including up to 6 months after the last doseof IMP) or is a male who intends to father a child during their participation in thestudy (including up to 6 months after the last dose of IMP);
• Subject has known primary immunodeficiency or active tuberculosis or tests positivefor acquired human immunodeficiency virus;
• Subject who tests positive for hepatitis B surface antigen (HBVsAg) or hepatitis Cribonucleic 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 priorsurgery;
• Subject has a mean QT interval corrected for heart rate using Bazett's (QTcB) orFridericia's (QTcF) correction ≥ 500 ms calculated from 3 consecutive 12-lead ECGs atScreening;
• Subject with an uncontrolled concurrent illness including, but not limited to, ongoingor active infection, significant hepatic disease (subjects with liver metastases whomeet the inclusion criteria will be allowed ), pneumonitis, symptomatic congestiveheart failure, uncontrolled hypertension, unstable angina pectoris, cardiacarrhythmia, interstitial or other current severe lung disease including poorlycontrolled chronic obstructive pulmonary disease, malabsorption or protracteddiarrhea, or psychiatric illness/social situations that would limit compliance withstudy requirement or compromise the ability of the subject to give written informedconsent;
• Subjects with Gilbert's syndrome;
• Subject with known active CNS metastasis, except primary brain tumors. Subjects withasymptomatic brain metastases or spinal cord compression who have been treated, areconsidered stable, and have not received steroid doses > 10 mg/day of prednisoloneequivalent 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 withstandard therapies such as antihistamines, 5-hydroxytryptamine antagonists, orcorticosteroids;
• Subject with a history of organ transplant or allogeneic bone marrow transplant;
• Subject currently using or have received immunosuppressive medications within 14 daysprior to the first dose of KHK2455, with the exception of topical or systemiccorticosteroids that are not to exceed 10 mg/day of prednisone or equivalent;
• Subject with a history of autoimmune disease (e.g., ulcerative colitis, Crohn'sdisease, 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 requiringsystemic treatment within the past 6 months are allowed;
• Subject who has a history of second primary cancer within the past 5 years, with theexception of:
• Curatively resected non-melanoma skin cancer;
• Curatively treated cervical intraepithelial neoplasia or prostate carcinoma withcurrent 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/orSponsor, would interfere with evaluation of the IMP or interpretation of the subject'ssafety or study results.