Clinical trial NCT05174637: A Study of FDA018-ADC in Patients with Advanced Solid Tumors
Official title: A PhaseⅠStudy to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of FDA018-ADC in Patients with Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced/ Metastatic Solid Tumors
Keywords: Trop-2
Solid tumor
TNBC
Antibody-drug conjugate, ADC
Lead sponsor: Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-01-03
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Primary outcomes:
measure: The dose limiting toxicity ( DLT)
timeFrame: From first dose to the end of Cycle 1, up to 35 days.
measure: The maximum tolerated dose (MTD)
timeFrame: From first dose to the end of Cycle 1, up to 35 days.
Secondary outcomes:
measure: Time to peak (Tmax)
timeFrame: Up to 17 weeks.
measure: Half-life time (t1/2)
timeFrame: Up to 17 weeks.
measure: Peak Plasma Concentration (Cmax)
timeFrame: Up to 17 weeks.
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Up to 17 weeks.
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From subject randomization up to 60 months.
measure: Objective Response Rate (ORR) according to RECIST 1.1
timeFrame: From subject randomization up to 60 months.
measure: Progression free survival(PFS) according to RECIST 1.1
timeFrame: From subject randomization up to 60 months.
measure: Duration of Response(DOR) according to RECIST 1.1
timeFrame: From subject randomization up to 60 months.
measure: Overall Survival (OS) according to RECIST 1.1
timeFrame: From subject randomization up to 60 months.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Jian Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
citation: Ponde N, Aftimos P, Piccart M. Antibody-Drug Conjugates in Breast Cancer: a Comprehensive Review. Curr Treat Options Oncol. 2019 Apr 1;20(5):37. doi: 10.1007/s11864-019-0633-6.
citation: Zaman S, Jadid H, Denson AC, Gray JE. Targeting Trop-2 in solid tumors: future prospects. Onco Targets Ther. 2019 Mar 1;12:1781-1790. doi: 10.2147/OTT.S162447. eCollection 2019.
citation: Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget. 2018 Jun 22;9(48):28989-29006. doi: 10.18632/oncotarget.25615. eCollection 2018 Jun 22.