A Study of FDA022-BB05 in Subjects With Advanced Solid Malignant Tumors

Study Overview
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Brief Summary
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This is a Phase 1, open-label and two-part study to evaluate the safety, tolerability, pharmacokinetics and efficacy of FDA022-BB05 in participants with advanced/metastatic solid malignant tumors.

Detailed Description
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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 FDA022-BB05 in patients with advanced/metastatic solid tumors. FDA022-BB05 is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify dose-limiting toxicities（DLT）and the maximum tolerated dose (MTD) through Day1 and Day 21 (cycle 1) with 1 dose. In addition, the recommended Phase II dose of FDA022-BB05 will be determined.

Official Title
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A PhaseⅠStudy to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of FDA022-BB05 in Subjects With Advanced Solid Malignant Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: FDA022 Monoclonal antibody-drug conjugate for injection


Participation Criteria
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Eligibility Criteria
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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; During the screening period, the patients should meet the following requirements: Absolute value of neutrophils ≥ 1.5 × 109/L, Platelet ≥ 100 × 109/L, Hemoglobin ≥ 90 g/L (no blood transfusions and no use of CSF in 2 weeks); The internationally standardized ratio (INR), prothrombin time (PT) and activated partial thrombin time (APTT) ≤1.5 × ULN; Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN); Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × ULN, AST/ALT ≤ 5 × ULN for liver metastasis; Serum creatinine≤ 1.5×ULN，or Ccr ≥60 mL/min calculated by Cockcroft and Gault formula; Preferential subjects with measurable lesion in Part 1. and subjects with at least one measurable lesion in Part 2; All acute toxicity of previous anti-tumor treatment or surgery is relieved to baseline severity or NCI CTCAE version 5.0 ≤ 1; Eligible fertile female participants or male participants with fertile female sexual partners must agree to use an effective method of contraception from the study initiation until at least 6 months after the last treatment; Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment. 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 in Part 1; Pathologically confirmed advanced/unresectable or metastatic breast cancer with HER2 overexpression that failed with one or more prior HER2 targeted therapy in Cohort A of Part 2; Pathologically confirmed advanced/unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression that failed with two or more prior HER2 targeted therapy in Cohort B of Part 2. 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 positive human immunodeficiency virus (HIV) antibody, active hepatitis C (antibody positive with HCV RNA positive), active hepatitis B (positive hepatitis B virus surface antigen with HBV-DNA titer higher than the upper limit of the reference range); 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FDA022-BB05<br>phase Ia: Participants with locally advanced or metastatic tumor will be administered FDA022-BB05 intravenously once at escalated doses in each cycle (of 21 days) during Phase Ia part of the study until disease progression or intolerable toxicity. phase Ib: Cohort expansion, Recommended doses from phase Ia. | Drug: FDA022 Monoclonal antibody-drug conjugate for injection<br>* FDA022-BB05, intravenously infusion, q3w<br>* Other names: FDA022-BB05;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | DLT will be assessed according to NCICTCAE v5.0. | Cycle 1 (21Days) | 
| Maximum tolerated dose (MTD） | MTD will be defined as the maximum dose level at which no more than 1 of 3 patients experience a DLT within cycle1 (21 days) of DLT observing period. | Cycle 1 (21 Days) | 
| Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs) | The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0. | Up to 3 years | 
| RP2D | the recommended phase II dose | Cycle1 (21 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) characteristics, Cmax | Peak Plasma Concentration | From cycle1 to Cycle10 (each cycle is 21 days. ) | 
| Pharmacokinetic (PK) characteristics, Tmax | Time of peak plasma concentration | From cycle1 to Cycle10 (each cycle is 21 days. ) | 
| Pharmacokinetic (PK) characteristics，AUC | Area under the plasma concentration versus time curve | From cycle1 to Cycle10 (each cycle is 21 days. ) | 
| Pharmacokinetic (PK) characteristics, t1/2 | Half-life time | From cycle1 to Cycle10 (each cycle is 21 days. ) | 
| Pharmacokinetic (PK) characteristics, CL/F | apparent Clearance | From cycle1 to Cycle10 (each cycle is 21 days. ) | 
| ADA | Anti-drug antibody | Up to 18 months | 
| ORR | Objective Response Rate | Up to 18 months | 
| PFS | Progression-free survival | Up to 18 months | 
| DoR | Duration of response | Up to 18 months | 
| OS | Overall survival rate | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumors, phase 1, oncology, HER2, Antibody drug conjugate (ADC)