Study of MT-8421 as Monotherapy and in Combination With Nivolumab in Patients With Selected Advanced Solid Cancer Types

Inclusion Criteria

• •Histologically confirmed, unresectable, locally advanced, or metastatic melanoma, HCC, NSCLC, RCC, MSI-H/dMMR malignancies, urothelial carcinoma, esophageal squamous cell carcinoma, mesothelioma, SCCHN, or cervical carcinoma not amenable to standard treatment, or standard treatment is not available, or in the Investigator's opinion, the standard treatment would not be in the patient's best interest.
• •Part A only: Evaluable only or measurable disease according to RECIST v1.1 Part B only: At least 1 measurable tumor lesion according to RECIST v1.1
• •Prior treatment must include a PD-1 or programmed cell death - ligand 1 (PD-L1) inhibitor. Prior treatment with a CTLA-4 inhibitor is not required.
• •Eastern Cooperate Oncology Group (ECOG) performance score of 0 or 1
• •Adequate bone marrow function, as determined by:
• •* Absolute neutrophil count (ANC) ≥ 1500/ μL (should not have received growth factors within 2 weeks prior to screening)
• •* Platelet count ≥ 75,000/ μL
• •* Hemoglobin ≥ 8.0 g/dL (no red blood cell transfusion within 2 weeks of study treatment start is allowed)
• •Adequate renal function, based on estimated creatinine clearance (eCrCl) ≥ 50 mL/min, calculated by the Cockcroft-Gault equation.
• •Adequate hepatic function, as determined by:
• •* Total bilirubin ≤ 1.5x upper limit of normal (ULN) or ≤ 2x ULN direct bilirubin for patients with Gilbert's Syndrome
• •* Aspartate transaminase (AST) ≤ 3x ULN (or ≤ 5x ULN if liver metastasis or HCC).
• •* Alanine transaminase (ALT) ≤ 3x ULN (or ≤ 5x ULN if liver metastasis or HCC).
• •* Adequate serum albumin (albumin ≥ 2.5 g/dL)
• •Availability of a lesion that can be biopsied with acceptable risk.
• •Patients capable of bearing children must have a negative highly sensitive pregnancy test within 72 hours before the start of treatment. Patients who are postmenopausal (\> 1 year since last menstrual cycle) or permanently sterilized (e.g., bilateral tubal occlusion, hysterectomy, bilateral salpingectomy) may be considered as not of reproductive potential.
• •Patients of reproductive potential must agree either to abstain continuously from heterosexual intercourse or to use a highly effective birth control method from signing the informed consent form (ICF) until 30 days after the last dose of MT-8421 and/or 5 months after the last dose of nivolumab for patients capable of bearing children and until 90 days after the last dose of MT-8421 for patients capable of fathering a child. Patients must not donate sperm during the study and for 90 days after the last dose of nivolumab or MT-8421.
• •* Received radiotherapy or another appropriate therapy for the CNS metastases, if clinically Indicated
• •* Have stable CNS disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the ICF compared with prior neuroimaging.
• •History or current evidence of significant cardiovascular disease before the start of treatment.
• •Current evidence of active, uncontrolled hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV) (evidenced by detectable viral load by polymerase chain reaction) or acquired immunodeficiency syndrome (AIDS)-related illness.
• •* Serology and virology measurements are not required to be performed at screening, but any previously reported results should be used for eligibility purposes. Investigators will test per their discretion
• •* Patients with a history of treated hepatitis C and non-quantifiable hepatitis C virus- ribonucleic acid (RNA) may be enrolled.
• •Patients with unintentional weight loss greater than 10% of their body weight over the preceding 2 months or less prior to first dose in the first cycle.