Advanced solid tumors
Conditions
Interventions
Experimental group:Arm 1:Sirolimus for Injection (albumin-bound) + DP303c
Experimental group:Arm 2:Sirolimus for Injection (albumin-bound) + SYS6043
Experimental group:Arm 3:Sirolimus for Injection (albumin-bound) + SYS6002
Experimental group:Arm 4:Sirolimus for Injection (albumin-bound) + SYS6010
Experimental group1:Sirolimus for Injection (albumin-bound) + DP303c
control group1:DP303c
Experimental group2:Sirolimus for Injection (albumin-bound) +SYS6043
Experimental group2:SYS6043
Experimental group3:Sirolimus for Injection (albumin-bound) +SYS6002
Control group3:SYS6002
Experimental group4:Sirolimus for Injection (albumin-bound) +SYS6010
Control group4:SYS6010
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Subjects aged 18 to 75 years (inclusive). 2. Patients with advanced solid tumors that are unresectable or metastatic and confirmed by histology or cytology. a. The Phase Ib dose escalation phase requires patients who have failed or are intolerant to standard therapy, lack standard treatment options, or refuse standard therapy; b. The Phase Ib PK expansion phase and Phase II require patients who have failed at least one prior line of therapy. Population requirements for different combination therapy groups are as follows: DP303c Combination Group: Patients with unresectable locally advanced recurrent or metastatic breast cancer who have failed treatment with anti-HER2 TOP1-ADC therapies such as DS8201, or other potentially eligible populations as determined through sponsor-investigator consultation. Combination with SYS6043: Patients with HR+/HER2- locally advanced or metastatic breast cancer eligible for first-line chemotherapy (specific requirements below), or other potentially eligible populations as determined by mutual agreement between the sponsor and investigators; i. HR+/HER2-, unresectable locally advanced or metastatic breast cancer patients; ii. No prior systemic chemotherapy for locally advanced, recurrent, or metastatic disease; iii. Researcher assessment indicating no further benefit from endocrine therapy and suitability for first-line chemotherapy. Combination with SYS6002 group: a) HER2- patients with unresectable locally advanced recurrent or metastatic breast cancer who have failed TOP1-ADC therapy, or b) Patients with recurrent/metastatic cervical cancer who have failed first-line standard therapy, or c) Patients with platinum-resistant advanced ovarian cancer, primary peritoneal cancer, and fallopian tube cancer, or d) Other potentially eligible populations as determined by the sponsor and investigator. Combination with SYS6010 group: HER2-negative, unresectable locally advanced recurrent or metastatic breast cancer, or other potentially eligible populations as determined by mutual agreement between the sponsor and investigators. c. HER2 expression is required for the combination with DP303c group, and EGFR expression is required for the combination with SYS6010 group. 3. At least one measurable lesion, as defined by RECIST 1.1 criteria. 4. ECOG performance status of 0 or 1. 5. Expected survival >= 3 months. 6. Major organ function must meet the following requirements within 7 days prior to enrollment: a. Complete Blood Count (CBC) (no blood transfusion, hematopoietic growth factors, erythropoietin, thrombopoietin, or other drugs to correct blood cell counts within 14 days before first dose): Absolute Neutrophil Count (ANC) >=1.5×10^9/L; Platelet count (PLT) >=100×10^9/L; Hemoglobin (HGB) >=90 g/L. b. Blood biochemistry: Serum creatinine (Cr) =30 g/L. Serum triglycerides <300 mg/dL or <3.42 mmol/L; serum cholesterol <350 mg/dL or <9.07 mmol/L. Glycated hemoglobin < 8%; c. Coagulation function: Activated partial thromboplastin time (APTT) and international normalized ratio (INR) <= 1.5×ULN (without anticoagulant therapy; patients receiving anticoagulant therapy must be within therapeutic target range and on stable dosage). 7. Willing to provide archived
Exclusion criteria
Exclusion criteria: 1. Previous treatment with antibody-drug conjugates (ADCs) of similar payloads (not required during the Phase Ib dose escalation phase). Patients must be excluded from combination therapy with DP303c or SYS6002 if they have previously received antibody-drug conjugates with tubulin inhibitors as the payload. Patients must be excluded from combination therapy with SYS6043 or SYS6010 if they have previously received antibody-drug conjugates with topoisomerase I inhibitors as the payload. 2. Subjects who have not completed the required washout period (prior to the first dose of study drug) following prior medications or treatments must be excluded. Classification Treatment Surgery Major Surgery/Major Organ Surgery (excluding puncture procedures) >=4 weeks Minimally invasive procedures (e.g., colostomy), excluding procedures or surgeries that can be recovered from within 14 days prior to the first dose and are assessed by the investigator as having recovered, such as tumor biopsy. >=2 weeks Radiotherapy Curative radiotherapy, or palliative radiotherapy to the chest =4 weeks Other palliative radiotherapy >=2 weeks Anticancer drug therapy Nitrosourea or Mitomycin C >=6 weeks Cytotoxic chemotherapy, biological therapy, or immunotherapy >=4 weeks Oral fluorouracil derivatives, traditional Chinese medicines with antitumor indications, small-molecule targeted therapies, endocrine therapy =2 weeks Combination drug therapy Glucocorticoids (prednisone >10 mg/day or equivalent doses of other glucocorticoids), except for the use of corticosteroids targeting local inflammation and for preventing allergies, nausea, and vomiting. >=2 weeks Intravenous administration of antibiotics, antifungal agents, or antiviral drugs >=2 weeks Others Localized treatment, such as ablation or interventional procedures >=2 weeks Thoracic effusion, ascites, or pericardial effusion drainage >=2 weeks Investigational/Unapproved Medicinal Product >=4 weeks attenuated live vaccine >=4 weeks CYP3A4 potent inducer or inhibitor >=2 weeks OATP1B1 and OATP1B3 inhibitors (applicable to combination with SYS6010 and SYS6043) >=2 weeks 3. Concurrently enrolled in another clinical study, unless it is an observational (non-interventional) clinical trial or they are in the follow-up period of an interventional trial. 4. Cumulative prior exposure to anthracycline-based drugs reaching the following doses: doxorubicin or liposomal doxorubicin > 500 mg/m²; epirubicin > 900 mg/m²; mitoxantrone > 120 mg/m²; Other (i.e., liposomal doxorubicin or other anthracyclines > equivalent to 500 mg/m² of doxorubicin); if more than one anthracycline is used, the cumulative dose must not exceed the equivalent of 500 mg/m² of doxorubicin (applies only to combination with DP303c). 5. During prior treatment with trastuzumab or structurally similar agents, LVEF decreased to <40%, symptomatic congestive heart failure (CHF) developed, or related toxicity occurred leading to permanent discontinuation of trastuzumab or structurally similar agents (applicable only to the combination with DP303c group); 6. Toxicity from prior antitumor therapy has not resolved to <= Grade 1 per NCI CTCAE V5.0 criteria or baseline levels (excluding toxicity deemed safe by the investigator, such as alopecia, hyperpigmentation, or functional impairment). 7. History of other malignant tumors within the past three years or concurrent active malignant tumors (excluding cured localized tumors such as basal cell carcinoma, squamo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence and frequency of adverse events (AEs) and serious adverse events (SAEs) in Phase ?b;Dose limiting toxicities (DLT) in Phase ?b ;The recommended phase 2 dose (RP2D) in Phase ?b ;Overall response rate (ORR) in Phase ?; | — |
Secondary
| Measure | Time frame |
|---|---|
| The incidence and frequency of AEs and SAEs in Phase ? Description: ;objective response rate (ORR) in Phase ?b;Disease control rate (DCR);Duration of response (DOR);Progression-free survival (PFS) ;Overall survival (OS);Blood concentration of DP303c;Blood concentration of SYS6043;Blood concentration of SYS6002;Blood concentration of SYS6010 ;Blood concentration of sirolimus ;Anti-drug antibodies (ADA) related to DP303c;ADA related to SYS6043;ADA related to SYS6002 ;ADA related to SYS6010; | — |
Countries
China
Contacts
Public ContactZhang Jian
Fudan University Shanghai Cancer Center
Outcome results
None listed