AMT-116 in Patients with Solid Tumors

Phase 1/2 Study of AMT-116 in Patients with Advanced Solid Tumors

The purpose of this study is to evaluate the safety and efficacy of AMT-116 monotherapy in subjects with advanced solid tumors. The study is divided into two parts: the part I is dose escalation and the Part Ⅱ for expansion.

Inclusion Criteria:

1. Patients must be willing and able to sign the ICF, and to adhere to the study visit schedule and other protocol requirements.
2. Age ≥18 years (at the time consent is obtained).
3. Patients with histologically confirmed, unresectable advanced solid tumor. Preferred tumor types include non-small cell lung, head and neck, esophageal, cervical, breast, bladder, gastric, biliary tract, skin squamous cell, liver, and basal cell cancer.
4. Patients who have undergone at least one systemic therapy and have radiologically or clinically determined progressive disease during or after most recent line of therapy, and for whom no further standard therapy is available, or who are intolerable to standard therapy.
5. Patients must have at least one measurable lesion as per RECIST version 1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. The anticipated survival duration is no less than three months.
8. Patients must have adequate organ function
9. Women of child-bearing potential (WCBP) must consent to the use of two effective contraceptive methods during the study treatment period and for at least 12 weeks after the final administration of IMP
10. Women of child-bearing potential (WCBP) must have a negative serum pregnancy test within seven days preceding the initial administration of the investigational medicinal product (IMP).
11. Male patients must agree to use a latex condom, even if they had a successful vasectomy, while on study treatment and for at least 12 weeks after the last dose of the IMP.
12. Male patients must agree not to donate sperm, and female patients must agree not to donate eggs, while on study treatment and for at least 12 weeks after the last dose of the IMP.
13. Availability of tumour tissue sample (either an archival specimen or a fresh biopsy material) at screening.

Exclusion Criteria:

1. Prior therapy with ADC based on Top1 inhibitor.
2. Central nervous system (CNS) metastasis.
3. Active or chronic skin disorder requiring systemic therapy.
4. History of Steven's Johnson's syndrome or Toxic Epidermal Necrolysis syndrome.
5. Active ocular conditions requiring treatment or close monitoring, including, but not limited to: macular degeneration, papilledema, active diabetic retinopathy with macular oedema, wet age-related macular degeneration requiring intravitreal injections, or uncontrolled glaucoma.
6. Persistent toxicities from previous systemic anti-neoplastic treatments of Grade >1.
7. Systemic anti-neoplastic therapy within five half-lives or 21 days, whichever is shorter, prior to first dose of the IMP.
8. Radiotherapy to lung field at a total radiation dose of ≥20 Gy within 6 months, wide-field radiotherapy (e.g., > 30% of marrow-bearing bones) within 28 days.
9. Major surgery (not including placement of vascular access device or tumor biopsies) within 28 days prior to the first dose of the IMP, or no recovery from side effects of such intervention.
10. Significant cardiac disease, such as recent (within six months prior to first dose of the IMP) myocardial infarction or acute coronary syndromes (including unstable angina pectoris), congestive heart failure (New York Heart Association class III or IV), uncontrolled hypertension, uncontrolled cardiac arrhythmias.
11. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis (e.g., idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, etc.).
12. History of thromboembolic or cerebrovascular events, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis, or pulmonary emboli within six months prior to first dose of the IMP.
13. Acute and/or clinically significant bacterial, fungal or viral infection including hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV).
14. Administration of a live vaccine within 28 days prior to the administration of the first dose of the IMP.
15. Patients requiring concurrent treatment of strong inhibitors or inducers of cytochrome P450 3A4 enzyme (CYP3A4) within 2 weeks prior to the first dose and during the study treatment.
16. Known or suspected severe allergy/hypersensitivity (resulting in treatment discontinuation) to monoclonal antibodies.
17. Known or suspected intolerance to the components of the IMP.
18. Concurrent participation in another investigational therapeutic clinical trial.
19. Patients with known active alcohol or drug abuse.
20. Pregnant or breast-feeding females.
21. Mental or medical disorders that prevent patients from signing informed consent or complying with the study, or other severe acute or chronic medical or psychiatric disorders or abnormal laboratory results that may increase the risk associated with study participation or IMP administration or may interfere with the interpretation of study results and, in the investigator's judgment, make patients ineligible for enrollment in the study.
22. There was a history of malignant tumors other than the selected diagnosis within 5 years prior to the first administration of IMP