A Study of FDA022-BB05 in Advanced/Metastatic Solid Tumors

A Phase 2, Multicenter, Open-Label Study to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of FDA022-BB05 in Patients With Advanced/Metastatic Solid Tumors

This is an open-label, multicenter, Phase II study to evaluate the efficacy and safety of FDA022-BB05 for the treatment in locally advanced, unresectable, or metastatic patients with selected HER2 overexpressing/expressing solid tumors which are not eligible for curative therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: FDA022-BB05

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jian Zhang, MD; Phone Number: 85000 021-64175590; Email: syner2000@163.com

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
    • Contact: Jian Zhang, MD; Phone Number: 85000 021-64175590; Email: syner2000@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects fully understand and voluntarily participate in this study and sign informed consent.

Left Ventricular Ejection Fraction (LVEF) ≥ 50% within 28 days prior to first dose.

Eastern Cooperative Oncology Group performance status( PS) of 0 or 1. Life expectancy ≥ 3 months.

Histopathologically or cytologically confirmed advanced/unresectable or metastatic solid malignant tumors that is refractory to or intolerable with standard treatment, or for which no standard treatment is available:

Cohort A: Pathologically documented breast cancer that:

• Is unresectable or metastatic.
• Has a history of low HER2 expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested).
• For HR-positive participants, is documented refractory to endocrine therapy, defined as having progressed on at least 1 endocrine therapy and determined by the investigator that subject would no longer benefit from further treatment from endocrine therapy.
• Was never previously HER2-positive(IHC 3+ or IHC 2+/ISH+) on prior pathology testing or was historically HER2 IHC 0 only.

Cohort B: Pathologically documented endometrial cancer that:

• Is unresectable or metastatic.
• Has a history of HER2 expression, defined as HER2 1+, 2+, or 3+ score on immunohistochemistry (IHC).
• Have had at least one prior line of platinum-based therapy (in any setting).
• Was never previously received other ADC anti-tumor treatment.

Cohort C: Metastatic or advanced solid tumor that are HER2 overexpression or mutation(Including urothelial cancer, colorectal adenocarcinoma and non-small cell lung cancer).

Exclusion Criteria:

• A treatment history of antibody-drug conjugate containing topoisomerase I inhibitors.

Subjects with one of the following conditions prior to first dose, including, but not limiting to：A major operation or severe trauma history within 4 weeks; A history of chemotherapy, targeted therapy, anti-angiogenesis therapy, biotherapy, immunotherapy, radiotherapy or other anti-tumor therapy within 4 weeks; A history of endocrine therapy within 3 weeks; A history of autologous stem cell transplant within 3 months.

Subjects with other malignant tumors in the past three years (not including cured non-melanoma skin basal cell carcinoma, cervical carcinoma in situ and other malignancies of low malignant potential that have been effectively controlled without treatment).

Subjects with symptomatic CNS metastasis (for example, cerebral edema requiring glucocorticoids therapy, or progressive CNS metastasis), not including prior cerebral and meningeal metastasis that is confirmed stable with MRI and without systematic glucocorticoids therapy.

Adverse reactions from the previous anti-tumor treatment have not yet recovered (>Grade 2 in NCI-CTCAE 5.0, with exception of alopecia and pigmentation or other adverse reactions judged no safety risk by the investigator).

Subjects with clinically significant cardiovascular or cerebrovascular disease, including, but not limiting to:

a medical history of symptomatic Congestive Heart Failure (CHF) (NYHA classes II-IV) or serious cardiac arrhythmia.

a medical history of myocardial infarction or unstable angina within 6 months prior to screening; a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females.

Subjects with a medical history of interstitial lung disease (ILD)/pneumonia in need of glucocorticoids intervention，or with interstitial lung disease, or suspicious ILD by imaging detection at screening.

Subjects with any uncontrolled active infection within 1 week prior to first dose.

Subjects with concomitant disease potentially increasing toxicological risk. Known allergy to protein preparation or any protein drug with similar structure to FDA022-BB05.

Subjects with a History of alcohol abuse or psychotropic/narcotic drug abuse; Pregnant or lactating women. Subjects with poor compliance, or not suitable for this study as determined by the investigator due to other reasons.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HER2 Low Metastatic/Recurrent Breast Cancer; Enrolled Subjects will receive a 5.4 mg/kg IV dose of FDA022-BB05 on Day 1 of each cycle Q3W	Drug: FDA022-BB05; Monoclonal antibody-drug conjugate for injection
Experimental: HER2 Expressing Metastatic/Recurrent Endometrial Cancer; Enrolled Subjects will receive a 5.4 mg/kg IV dose of FDA022-BB05 on Day 1 of each cycle Q3W	Drug: FDA022-BB05; Monoclonal antibody-drug conjugate for injection
Experimental: HER2 Overxpressing/Mutant Metastatic/Recurrent Solid tumor; Enrolled Subjects will receive a 5.4 mg/kg IV dose of FDA022-BB05 on Day 1 of each cycle Q3W	Drug: FDA022-BB05; Monoclonal antibody-drug conjugate for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The percentage of patients with CR and PR assessed by investigators according to RECIST v 1.1	up to 24 month
Occurrence of adverse events (AEs) and serious adverse events (SAEs)	Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0.	up to 24 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DoR)	DOR is defined as the time from the date of first documented response until the date of documented progression or death.	up to 24 month
Disease control rate (DCR)	DCR is the percentage of subjects who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD).	up to 24 month
Progression free survival (PFS)	PFS is the time from date of first dose of study treatment until the date of objective disease progression or death.	up to 24 month
Overall survival (OS)	OS is the time from date of first dose of study treatment until death due to any cause.	up to 24 month
Pharmacokinetic (PK) Analysis: Area Under the Concentration Versus Time Curve (AUC) of Serum FDA022-BB05 Following First Dose	The serum PK parameters of FDA022-BB05 and its analytes for area under the concentration-versus-time curve from time 0 to the last quantifiable concentration as calculated by the linear-up log-down trapezoidal method (AUClast) and AUC from time 0 to infinity (AUCinf) elimination rate constant associated with the terminal phase were estimated using standard non-compartmental methods.	From cycle1 to Cycle10 (each cycle is 21 days. )
Pharmacokinetic Analysis: Maximum (Peak) Observed Serum Concentration (Cmax) of Serum FDA022-BB05 Following First Dose	The serum PK parameters Maximum (peak) Observed serum concentration of FDA022-BB05 and its analytes were estimated using standard non-compartmental method.	From cycle1 to Cycle10 (each cycle is 21 days. )
Pharmacokinetic Analysis: Time of Maximum Plasma Concentration (Tmax) of Serum FDA022-BB05 Following First Dose	The serum PK parameters of Time of maximum plasma concentration (Tmax) for FDA022-BB05 and its analytes were estimated using standard non-compartmental methods.	From cycle1 to Cycle10 (each cycle is 21 days. )
Pharmacokinetic Analysis: Terminal Elimination Half-life (t1/2) of Serum FDA022-BB05 Following First Dose	The serum PK parameters of Terminal elimination half-life for FDA022-BB05 and its analytes was estimated using standard non-compartmental methods.	From cycle1 to Cycle10 (each cycle is 21 days. )
Number of participants who developed measurable anti-drug antibodies	Individual participant data and descriptive statistics will be provided for data at each time point.	up to 24 month

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): May 13, 2024
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: May 8, 2024
• First Submitted That Met QC Criteria: May 12, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: F0034-201

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