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

A PhaseⅠStudy to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced/ Metastatic Solid Tumors
• Intervention / Treatment: Drug: FDA018-ADC

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. The expansion phase enrolled patients into three cohorts defined by tumor type: cohort 1 included patients with locally advanced or metastatic TNBC; cohort 2 included patients with non-small-cell lung cancer (NSCLC); and cohort 3 included those with other locally advanced or metastatic solid tumors. The efficacy and safety, as well as the recommended phase 2 dose (RP2D) were determined in this phase.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FDA018-ADC A mg/kg; Subjects will receive FDA018-ADC A mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.	Drug: FDA018-ADC; Subjects will receive an intravenous infusion of FDA018-ADC until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.; Other Names: FDA018-Antibody-drug Conjugate; F0024
Experimental: FDA018-ADC B mg/kg; Subjects will receive FDA018-ADC B mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.	Drug: FDA018-ADC; Subjects will receive an intravenous infusion of FDA018-ADC until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.; Other Names: FDA018-Antibody-drug Conjugate; F0024
Experimental: FDA018-ADC C mg/kg; Subjects will receive FDA018-ADC C mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.	Drug: FDA018-ADC; Subjects will receive an intravenous infusion of FDA018-ADC until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.; Other Names: FDA018-Antibody-drug Conjugate; F0024
Experimental: FDA018-ADC D mg/kg; Subjects will receive FDA018-ADC D mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.	Drug: FDA018-ADC; Subjects will receive an intravenous infusion of FDA018-ADC until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.; Other Names: FDA018-Antibody-drug Conjugate; F0024
Experimental: FDA018-ADC E mg/kg; Subjects will receive FDA018-ADC E mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.	Drug: FDA018-ADC; Subjects will receive an intravenous infusion of FDA018-ADC until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.; Other Names: FDA018-Antibody-drug Conjugate; F0024
Experimental: FDA018-ADC F mg/kg; Subjects will receive FDA018-ADC F mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.	Drug: FDA018-ADC; Subjects will receive an intravenous infusion of FDA018-ADC until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.; Other Names: FDA018-Antibody-drug Conjugate; F0024
Experimental: FDA018-ADC G mg/kg; Subjects will receive FDA018-ADC G mg/kg of body weight via intravenous (IV) infusion on Day 1 of a 14-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle n) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle(Cycle 1 ~ Cycle n) in dose expansion phase, until the date of first documented progression or unacceptable toxicity or death.	Drug: FDA018-ADC; Subjects will receive an intravenous infusion of FDA018-ADC until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.; Other Names: FDA018-Antibody-drug Conjugate; F0024

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The dose limiting toxicity ( DLT)	Evaluated according to NCI CTCAE V5.0	From first dose to the end of Cycle 1, up to 35 days.
The maximum tolerated dose (MTD)	Maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 or more in a cohort of either 3 or 6 patients experiences a dose limiting toxicity (DLT) attributed to FDA018.	From first dose to the end of Cycle 1, up to 35 days.
Objective Response Rate (ORR) according to RECIST 1.1	ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) according to RECIST1.1. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to <10 mm. PR was defined as ≥ 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters.	From subject randomization up to 60 months.
Adverse Events	To check the numbers of AEs happened during the course of trial.	From subject randomization up to 60 months
Recommended phase II dose (RP2D)		From subject randomization up to 60 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to peak (Tmax)	Tmax of Total Antibody, Total SN-38, Free SN-38, SN-38 Glucuronide and FDA018-ADC will be measured.	Up to 17 weeks.
Half-life time (t1/2)	t1/2 of Total Antibody, Total SN-38, Free SN-38, SN-38 Glucuronide and FDA018-ADC will be measured.	Up to 17 weeks.
Peak Plasma Concentration (Cmax)	Cmax of Total Antibody, Total SN-38, Free SN-38, SN-38 Glucuronide and FDA018-ADC will be measured.	Up to 17 weeks.
Area under the plasma concentration versus time curve (AUC)	AUC of Total Antibody, Total SN-38, Free SN-38, SN-38 Glucuronide and FDA018-ADC will be measured.	Up to 17 weeks.
Number of subjects who develop detectable anti-drug antibodies (ADAs)	The subject's ADA positive rate will be assessed By ELISA.	From subject randomization up to 60 months.
Progression free survival(PFS) according to RECIST 1.1	Progression-free survival (PFS) was defined as the interval from the first dose start date to the date of disease progression defined as documented progressive disease (PD) or death from any cause, whichever occurs first.	From subject randomization up to 60 months.
Duration of Response(DOR) according to RECIST 1.1	Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).	From subject randomization up to 60 months.
Overall Survival (OS) according to RECIST 1.1	Overall survival was defined as the time from the date of the first dose start date to the date of death due to any cause.	From subject randomization up to 60 months.

Collaborators and Investigators

• Sponsor: Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jian Zhang, Doctor, Fudan University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): January 3, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Solid tumor; TNBC; Trop-2; Antibody-drug conjugate, ADC
• Additional Relevant MeSH Terms: Neoplasms; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates
• Other Study ID Numbers: F0024-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No