Advanced/Metastatic Solid Tumors
Conditions
Interventions
SYS6043 -Phase Ia phase (dose escalation):The starting dose of SYS6043 is set at 1.2 mg/kg, with a pre-set maximum ascending dose of 10.0 mg/kg, administered by intravenous infusion every 3 weeks (Q3W
SYS6043 -Phase Ia phase (PK amplification):Over the course of the dose escalation study, the number of PK cases continued in the 2-4 dose groups (<=MTD dose level) recommended after SMC assessment.
SYS6043 -Phase Ib cohort expansion phase:Based on the results of Phase Ia dose escalation and PK amplification, 1-2 dose groups recommended by SMC evaluation will be used as the recommended dose (RP2D
Sponsors
Ethics Committee of Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Unless otherwise noted, the inclusion criteria listed below apply to both Phase Ia and Phase Ib studies. Participants must meet all of the following criteria to be selected: 1. Age 18-75 (inclusive) years old (subject to the day of signing the informed consent form). 2. Histologically or cytologically confirmed advanced/unresectable or metastatic solid tumors with disease recurrence or progression during or after standard systemic therapy, or intolerance to standard therapy for which no standard therapy is available. 3. At least one measurable lesion according to the Efficacy Evaluation Criteria for Solid Tumors (RECIST v1.1). Participants with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases will discuss the evaluation with the sponsor's medical monitor on a case-by-case basis before determining whether they are suitable for enrollment. 4. Participant expected survival>= 3 months. 5. ECOG score 0-1 with no score deterioration found within 28 days prior to enrollment. 6. ECHO or MUGA within 28 days prior to enrollment showing LVEF>=50%. 7. Vital organ function meeting the following requirements within 7 days prior to enrollment: a. Routine blood count (no whole blood, red blood cells, platelet transfusions within 7 days prior to sampling, and no drugs such as hematopoietic stimulating factor [G-CSF or GM-CSF], erythropoietin [EPO], thrombopoietin [TPO] to correct blood cell count): Neutrophil count ANC >=1.5×109/L; Platelet count PLT >=100×109/L; Hemoglobin HGB >=9 g/dL. b. Blood biochemistry: Creatinine clearance should be >=60 mL/min (calculated according to the Cockcroft-Gault formula); ? Serum total bilirubin TBIL = 30 g/L. c. Coagulation function: Activated partial thromboplastin time (APTT) and international normalized ratio (INR) =3 weeks (5-fluorouracil, leucovorin, and/or weekly paclitaxel treatment >=2 weeks) nitrosourea or mitomycin C treatment >=6 weeks Tyrosine kinase inhibitor (TKI) >=1 week Small molecule targeted drugs (except TKIs) >=5 half-lives Chloroquine/hydroxychloroquine >=2 weeks Immunotherapy >=4 weeks Hormone therapy >=2 weeks, except for gonadotropin-releasing hormone (GnRH) agonists or antagonists for the treatment of prostate cancer, breast cancer, or oral contraceptives Anti-tumor TCM >=2 weeks Major surgery >=4 weeks (or 2 weeks for low-invasive cases [e.g., colostomy]), excluding procedures or procedures that can be recovered within 14 days prior to the first dose and considered to have resumed as assessed by the investigator, e.g., tumor biopsy Radiotherapy >=4 weeks (radical radiation therapy, or palliative radiation therapy to the chest) >=2 weeks (palliative radiotherapy to other sites [inclu
Exclusion criteria
Exclusion criteria: Unless otherwise noted, the following exclusion criteria apply to both Phase Ia and Phase Ib studies. Participants who meet any of the following criteria will be excluded from this study: 1. Prior treatment with B7-H3 targeted therapy. 2. Prior treatment with topoisomerase inhibitor antibody conjugates (e.g., trastuzumab). 3. History of symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] Class II-IV) or severe arrhythmia requiring treatment. 4. History of myocardial infarction or unstable angina within 6 months prior to enrollment. 5. Mean QT interval (QTcF) corrected by Fredericia's formula for males and females lengthened to >470 milliseconds (ms) based on the results of three 12-lead electrocardiograms (ECGs). 6. Inability or unwillingness to discontinue concomitant medications known to prolong the QT interval. 7. Has a history of interstitial lung disease (e.g., non-infectious interstitial pneumonitis, pneumonia, pulmonary fibrosis, and severe radiation pneumonitis) or current interstitial lung disease or suspected of such disease by imaging at screening. 8. Has a history of underlying pulmonary disease, including but not limited to pulmonary embolism, severe asthma, severe COPD, restrictive lung disease, and other clinically significant lung impairment within 3 months prior to initiation of study treatment or the need for supplemental oxygen. 9. Any autoimmune, connective tissue disease, or inflammatory disease (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.) documented or suspected to involve the lungs at screening. 10. Presence of an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals. 11. Known human immunodeficiency virus (HIV) infection. 12. Participants with active viral (any etiology) hepatitis were excluded. However, participants with serological evidence of chronic hepatitis B virus (HBV) infection (defined as a positive hepatitis B surface antigen [HBsAg] test or a positive hepatitis B core antibody test), viral load below the limit of quantification (HBV DNA titer <1000cps/ml or 200IU/ml), and who are not currently receiving antiviral therapy may be eligible to participate in the study and should be discussed with the sponsor's medical monitor. However, for participants with a history of hepatitis C virus (HCV) infection, only those who have completed curative antiviral therapy and have a viral load below the limit of quantification are eligible for enrollment in the study. 13. Lactating females (females who are willing to temporarily interrupt breastfeeding will also be excluded), or those who have been confirmed to be pregnant by pregnancy examination within 7 days prior to enrollment. 14. Presence of spinal cord compression or clinically active brain metastases, defined as untreated, symptomatic, or requiring corticosteroids or anticonvulsants to control related symptoms. Participants with asymptomatic central nervous system metastases who have been on stable radiological and neurological disease for at least 4 weeks after receiving central nervous system-directed therapy and who are on stable or decreasing doses of corticosteroids (equivalent to <=10mg/day prednisone) are eligible for study entry. 15. Multiple primary malignancies within 3 years prior to enrollment, with the exception of adequately resected non-melanoma skin cancer (e.g., resected basal or squamous cell skin cancer), orthotopic disease that has received curative therapy (e.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety endpoints: Adverse events (AEs), serious adverse events (SAEs).;PK index: SYS6043 PK parameters of toxin-bound antibody (SYS6043), total antibody and free toxin (JS-1) after single and continuous administration: including but not limited to Cmax, Tmax, t1/2, AUClast, AUCinf, CL, Vss, Cmax, ss, Cmin, ss, AUCss, Rac, etc.;Occurrence and frequency of dose-limiting toxicities (DLTs).;Immunogenicity: incidence of anti-SYS6043 antibodies, titers, and neutralizing antibodies (if applicable);Effectiveness endpoints: objective response rate (ORR), disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), and overall survival (OS).;Laboratory test markers;Ancillary examination indicators: vital signs, electrocardiogram, ECOG score, echocardiography, physical examination, etc;Assessment of MTD and/or RP2D;B7-H3, PD-L1 protein expression levels and tumor-associated gene variants.; | — |
Countries
China
Contacts
Public ContactLi Zhang
Sun Yat-sen University Cancer Prevention Center
Outcome results
None listed