Advanced solid tumor
Conditions
Interventions
Dose-escalation group:SYS6023, administered by intravenous infusion, at a dose ranging from 0.5 to 6.5 mg/kg
Cohort-expansion A group:SYS6023, administered by intravenous infusion, recommended dosage (to be determined based on the dose-escalation group data )
Cohort-expansion B group:SYS6023, administered by intravenous infusion, recommended dosage (to be determined based on the dose-escalation group data )
Cohort-expansion C group:SYS6023, intravenous infusion, recommended dosage ( to be determined based on the dose-escalation group data)
Cohort-expansion D group:SYS6023, intravenous infusion, recommended dosage (to be determined based on the dose-escalation group data )
Cohort-expansion E group:SYS6023, intravenous infusion, recommended dosage (to be determined based on the dose-escalation group data )
Cohort-expansion F group:SYS6023, intravenous infusion, recommended dosage (to be determined based on the dose-escalation group data )
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age = 18 years; 2. Histologically and/or cytologically confirmed locally advanced unresectable or metastatic malignant solid tumor; 3. Sufficient archived or fresh tumor tissue samples must be provided for HER3 testing, among others; 4. Medical documentation must be provided before the first dose to clarify the following molecular typing information: HER2, HR receptor (including estrogen receptor (ER) and progesterone receptor (PR) ) expression for breast cancer participants, and EGFR mutation, ALK fusion, ROS1 fusion, BRAF V600 mutation, NTRK fusion, RET rearrangement, HER2 mutation, Met exon 14 skipping mutation, Met amplification, KRAS G12c mutation status for non-small cell lungcancer participants; 5. Depending on the trial phase, the following requirements must be met: - **Cohort Expansion Phase:** - **Cohort A:** HER3+ (by central lab), HR+/HER2- (HR+ defined as expressing estrogen receptor (ER), with or without progesterone receptor (PR) co-expression), locally advanced or metastatic breast cancer, previously treated with at least one line of systemic therapy including endocrine and CDK4/6 inhibitor treatment. - **Cohort B:** EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer, previously treated with at least one line of systemic therapy, including EGFR TKI and platinum-based chemotherapy. - **Cohort C:** HER3+ (by central lab), HER2+, locally advanced or metastatic breast cancer, previously treated with at least two lines of anti-HER2 systemic therapy including trastuzumab, taxane, and T-DM1 or TKI. **Cohort D:** HER3+ (by central lab), platinum-resistant recurrent ovarian cancer (defined as disease progression within >3 months and =6 months after last platinum-based chemotherapy for first-line, or within 6 months for second-line or higher lines of platinum-based chemotherapy), and non-platinum refractory (defined as disease progression within 4 weeks after last platinum-based chemotherapy). **Cohort E:** Other driver gene-positive (e.g., ALK fusion, ROS1 fusion, BRAF V600 mutation, NTRK fusion, RET rearrangement, HER2 mutation, Met exon 14 skipping mutation, Met amplification, KRAS G12c mutation, etc.), locally advanced or metastatic non-small cell lung cancer, previously treated with corresponding targeted TKI therapy. **Cohort F:** other HER3+ (by central lab) tumor types (including but not limited to TNBC, driver gene mutation-negative NSCLC, prostate cancer, etc.) which may potentially benefit from this treatment, or known NRG1 fusion tumors, both of which have previously treated with at least one line of systemic therapy. 6. At least one measurable lesion according to RECIST1.1 criteria; 7. ECOG performance status score of 0-1; 8. Expected survival of at least 3 months; 9. Adequate organ function, with laboratory test results meeting the following criteria (no blood transfusions, EPO, G-CSF, or other medical support treatments within 14 days before testing): ANC = 1.5 × 10^9/L PLT = 100 × 10^9/L Hemoglobin (Hb) = 90 g/L TBIL = 1.5 × ULN, or TBIL = 3 × ULN for participants with liver metastasis, liver cancer, or Gilbert's syndrome ALT and AST = 2.5 × ULN, or ALT and AST = 5 × ULN for participants with liver metastasis or liver cancer Creatinine clearance (Ccr) > 50 mL/min (calculated using Cockcroft-Gault formula) Activated partial thromboplastin time (APTT) = 1.5 × ULN; INR = 1.5 × ULN Left ventricular ejection fraction (LVEF) = 50%
Exclusion criteria
Exclusion criteria: 1. Known symptomatic central nervous system or meningeal metastases, or other evidence of uncontrolled central nervous system or meningeal metastases as judged by the investigator; stable central nervous system or meningeal metastases are allowed; 2. Previous treatment with HER3-targeting ADC; 3. Adverse reactions from previous anti-tumor treatments that have not recovered to = Grade 1 according to CTCAE 5.0 (excluding toxicities deemed not a safety risk by the investigator, such as alopecia); 4. Receipt of antibody-based macromolecule therapy, definitive radiotherapy, immunotherapy within 28 days before the first dose, or chemotherapy, small molecule targeted therapy, palliative radiotherapy, hormone therapy, or traditional Chinese medicine with anti-tumor indication effects within 14 days or 5 half-lives (whichever is longer) before the first dose; 5. Concurrent participation in another clinical trial, unless it is an observational (non-interventional) clinical trial or in the follow-up period of an interventional trial; 6. Receipt of major surgery or invasive intervention within 28 days before the first dose; 7. Known severe allergic reactions to the investigational intervention or any of its components or excipients; 8. Active bacterial, fungal, or viral infection requiring intravenous antibacterial, antifungal, or antiviral treatment before the first dose. Participants receiving prophylactic infection treatment without active infection symptoms may be considered for inclusion; 9. Uncontrolled serous cavity effusion (e.g., pleural effusion, ascites, pericardial effusion, etc.) requiring frequent drainage or medical intervention within 7 days before the first dose, excluding exfoliation cytology of exudate; 10. History of immunodeficiency, including HIV antibody positivity; 11. HBsAg positive with HBV-DNA higher than the lower limit of detection or 1000 copies/mL (500 IU/mL) (whichever is lower), HCV antibody positive with HCV-RNA higher than the lower limit of detection or 1000 copies/mL (whichever is lower); 12. Severe cardiovascular disease history, including but not limited to: Severe cardiac arrhythmia or conduction abnormality requiring clinical intervention, such as ventricular arrhythmia, grade II-III atrioventricular block, etc.; Average QTcF > 450 ms on three resting 12-lead ECGs; Acute coronary syndrome, congestive heart failure, stroke, or other grade 3 or higher cardiovascular events within 6 months before the first dose; NYHA classification = Class II; Any factors increasing the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death in a first-degree relatives under 40 years old, concomitant use of drugs known to prolong QT interval; Uncontrolled hypertension (screening systolic BP = 160 mmHg and/or diastolic BP = 100 mmHg); 13. Drug-induced colitis, or history of hormone-requiring interstitial lung disease/pneumonitis or current suspicion of interstitial lung disease/pneumonitis on screening imaging; 14. Evidence of gastrointestinal bleeding or perforation risk, or pyloric obstruction, persistent recurrent vomiting (defined as vomiting = 3 times within 24 hours), deemed unsuitable for inclusion by the investigator; 15. Use of or need for strong CYP3A4 inducers or inhibitors, OATP1B1 or OATP1B3 inhibitors within 5 half-lives before the first dose or during the study; 16. Current
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of dose-limiting toxicity (DLT);Incidence and severity of AEs and SAEs;Description: Safety indicators including laboratory tests, vital signs, physical examination, ECG changes;Recommended Phase 2 Dose(RP2D); Objective response rate (ORR) of the Dose- Expansion Cohort; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters after single and multiple dosing of SYS6023;Immunogenicity parameters;Dose escalation group efficacy index(ORRDCRDoRPFSOS); | — |
Countries
China
Contacts
Public ContactShun Lu
Shanghai Chest Hospital
Outcome results
None listed