A Study of FDA018-ADC in Patients with Advanced Solid Tumors

This is a Phase 1, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and efficacy of FDA018-ADC in patients with advanced/metastatic solid tumors.

This is a first-in-human (FIH), Phase 1, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of FDA018-ADC in patients with advanced/metastatic solid tumors. FDA018-ADC is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD) and dose-limiting toxicities（DLT）during 35-day cycle with 3 doses. In addition, the maximum-tolerated dose and recommended Phase II dose for FDA018-ADC will be determined.

Eligibility Criteria:
Inclusion Criteria:

1. Patients able to give written informed consent;
2. Age ≥ 18 and ≤ 75 years old, male or female;
3. Patients have histological or cytological diagnosis with advanced solid tumors, cann't benefit from existing standard treatment options, and are not suitable for surgical resection or radiation therapy for the purpose of cure; tumor types in the study include: triple-negative breast cancer (TNBC), urothelial cancer (UC), non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, gastric adenocarcinoma, esophageal, ovarian, colorectal and so on.
4. Have measurable lesions defined in RECIST v. 1.1;
5. Expected survival ≥ 12 weeks;
6. Eastern Cancer Cooperative Group (ECOG) performance status 0-1;
7. Adequate bone marrow, hepatic, and renal function;
8. All acute toxicity of previous anti-tumor treatment or surgery is relieved to baseline severity or NCI CTCAE version 5.0 ≤ 1;
9. Tumor tissue sections available；
10. Patients of child bearing potential must agree to take contraception during the study and for 6 months after the last day of treatment.

Exclusion Criteria:

1. Previous treatments for anti-Trop-2 antibody or other treatments against Trop-2, such as IMMU-132;
2. Have history of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI toxicity to prior irinotecan, or previously allergic to macromolecular protein preparations;
3. Have had other malignant tumors in the past 5 years;
4. Received other anti-tumor treatments (including chemotherapy, radiotherapy, Targeted therapy, immunotherapy, experimental treatment and so on) within 4 weeks;
5. Infection requiring intravenous antibiotic use within 1 week or Fever of unknown cause occurred before the first administration\> 38.5℃；
6. Have CNS (central nervous system) metastasis with clinical symptoms;
7. Any of the following cardiac criteria:

   1. Known history of severe heart disease, such as CHF≥ level 2, NYHA≥ level 2 and angina requiring medication;
   2. Clinically significant cardiac arrhythmia requiring anti-arrhythmia therapy;
   3. Hypertension not controlled by medication;
8. Have history of clinical significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months;
9. Patients with poorly controlled diabetes;
10. Suffering from active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease), and history of intestinal obstruction, or GI perforation;
11. Patients who had undergone major surgery or severe trauma within 4 weeks prior to the first dose;
12. Patients who had undergone autologous within 3 months of initiation of study treatment or allogeneic organ or stem cell transplantation within 6 months of initiation of study treatment;
13. Clinically active bacterial, fungal or viral infections (eg active hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), syphilis positive and so on);
14. Patients who had undergone systemic high-dose steroids within 2 weeks of initiation of study treatment;
15. Occurrence of serious venous/venous thrombosis within 1 year prior to the first dose, such as cerebrovascular accidents (including transient ischemic attack), deep vein thrombosis and pulmonary embolism;
16. Patients have history of psychotropic drug abuse, alcohol or drug abuse；
17. Women who are pregnant or lactating；
18. Any condition that is unstable or may jeopardize patient safety and its compliance with the study;
19. Other circumstances that is deemed not appropriate for the study.