A Phase 1 Open-label, Multicenter, Dose-Ranging Study to Investigate Safety and Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of MT-6402 in Subjects with Advanced Solid Cancer That Expresses PD-L1

• Part B
  • Subjects without easily biopsied lesions (biopsy sites of non-significant risk, in the opinion of the Investigator) or unwilling to consent to baseline and end of Cycle 2 biopsy. Patients for whom a biopsy is not feasible must be discussed with the Medical Monitor.
  • Subjects unwilling to have baseline and on-study core biopsy (last 2 weeks of Cycle 2) performed.
• Parts A and B
  • History or current evidence of another neoplastic disease, except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively treated Stage I to II non-melanoma skin cancer or any previous cancer curatively treated > 2 years before the start of treatment.
  • Active autoimmune disease currently under treatment or required systemic treatment within 2 years (replacement therapy, e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed). Subjects who have not required systemic treatment of an autoimmune disease for at least 2 years may be enrolled if permission is provided after discussion with the Medical Monitor.
  • Ongoing > Grade 1 immune-related toxicity caused by prior CPI therapy (i.e., PD-1 inhibitors, PD-L1 inhibitors, or CTLA-4 inhibitors). Subjects with stable endocrinological AEs, e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or diabetes mellitus, must have been on a stable dose of supplemental therapy for at least 2 weeks before screening to be eligible for this study. History of repeat Grade 2 pneumonitis or carditis on previous CPI and/or Grade 3 immune-related adverse event on previous CPI treatment.
  • Evidence of active noninfectious ≥ Grade 2 pneumonitis or current evidence of ≥ Grade 3 other underlying pulmonary disease.
  • Received any of the following PD-L1 inhibitors within the following time periods prior to the first dose of MT-6402: atezolizumab – 12 months; durvalumab – 7 months; avelumab – 2 months.
  • Any concurrent cancer treatment, apart from local treatment of non-target lesions for palliative intent (e.g., local surgery or radiotherapy).
  • Prior radiation therapy within 4 weeks before the start of study treatment. NOTE: A lesion in a previously irradiated area can only be considered a target lesion if there has been radiographical disease progression since the end of radiation therapy.
  • Received approved or investigational treatment for the disease under study (except PD-L1 inhibitors where exclusion criterion 6 applies) within 4 weeks before the start of treatment. For small molecules (MW < 0.9 kDa), the washout is 5 half-lives, but at least 2 weeks.
  • Subjects who have had allogeneic tissue or solid organ transplantation.
  • Current evidence of new or growing central nervous system (CNS) metastases during screening. Subjects with known asymptomatic CNS metastases will be eligible if they meet all the following criteria:
    • Evidence of leptomeningeal metastasis.
    • Have stable CNS disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before screening compared with prior neuro imaging.
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the start of study treatment.
  • History or current evidence of significant cardiovascular disease before the start of treatment, including but not limited to the following conditions:
    • Angina pectoris requiring anti-anginal medication, (chest pain: Common Terminology Criteria for Adverse Events [CTCAE] Grade ≥ 2)
    • Clinically significant valvular disease.
    • Myocardial infarction within 12 months prior to the start of treatment.
    • Arterial thrombosis or pulmonary embolism within 3 months before the start of treatment.
    • History of Grade ≥ 2 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria Class ≥ II.
    • Left ventricular ejection fraction (LVEF) < 55%, assessed preferably by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan if ECHO is not available, within 28 days before starting study treatment.
    • High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > 100/min at rest and upon repeated testing, significant ventricular arrhythmia (CTCAE Grade ≥ 2 [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block]) or left ventricular bundle branch block. Subjects receiving digoxin, calcium channel blockers, or beta-adrenergic blockers are eligible at the Investigator’s discretion after consultation with the Medical Monitor if the dose has been stable for ≥ 2 weeks before the start of treatment with MT-6402.
    • Any of the following within 3 months before the start of treatment: pericarditis (any CTCAE Grade), pericardial effusion (CTCAE Grade ≥ 2), non-malignant pleural effusion (CTCAE Grade ≥ 2) or malignant pleural effusion (CTCAE Grade ≥ 3) (subjects with pleural effusion that is manageable and stable > 3 months prior to study are eligible).
    • QT interval correction for heart rate using Fridericia’s formula (QTcF) ≥ 470 ms (average from 3 QTcF values on the triplicate 12-lead electrocardiogram [ECG]) at screening. In subjects with right bundle branch blocks, additional corrections will be performed to calculate the QT equivalent JT, and depending on the result the subject may be eligible with the agreement of the Medical Monitor.
    • Current evidence of uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) at screening. Serology testing is not required if seronegativity is documented in the medical history, and if there are no clinical signs suggestive of HIV or hepatitis infections, or suspected exposure. The following exceptions apply for subjects with positive viral serology:
      • Subjects with HIV and an undetectable viral load and CD4 + T-cell (CD4+) counts ≥ 350 cells/mL may be enrolled but must be taking appropriate opportunistic infection prophylaxis, if clinically relevant.
      • Subjects with positive HBV serology are eligible if they have an undetectable viral load and the subject will receive antiviral prophylaxis for potential HBV reactivation per institutional guidelines.
      • Subjects with positive HCV serology are eligible if quantitative polymerase chain reaction (PCR) for plasma HCV RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
    • Current treatment requiring systemic steroids at doses > 10 mg/day prednisone equivalent.
    • Subjects with a history of hypersensitivity or serious toxic reactions to kanamycin or other aminoglycosides.
    • Subjects with unintentional weight loss > 10% of their body weight over the preceding 2 months or less before screening.
    • Subjects who are pregnant or breastfeeding.
    • History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Medical Monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

Prior treatment must include a CPI (i.e., PD-1 inhibitors or PD-L1 inhibitors with or without CTLA-4 inhibitors) if there is an approved CPI for the specific cancer type.