A Multicenter, Randomized, Controlled, Open-label, Phase II Study to Evaluate the Efficacy and Safety of SG001 in Combination With PLD in Patients With Platinum-resistant Relapsed Epithelial Ovarian Cancer
Overview
- Phase
- Phase 2
- Intervention
- SG001
- Conditions
- Epithelial Ovarian Cancer
- Sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Enrollment
- 126
- Primary Endpoint
- 1. Objective response rate (ORR, assessed by investigators according to RECIST 1.1 criteria)
- Last Updated
- 4 years ago
Overview
Brief Summary
This study is a multicenter, randomized, controlled, open-label, phase II study to evaluate the efficacy and safety of SG001 in combination with doxorubicin hydrochloride liposome injection in patients with platinum-resistant relapsed epithelial ovarian cancer.
Detailed Description
This is a multicenter, randomized, controlled, open-label, phase II clinical study to evaluate the efficacy and safety of SG001 in combination with doxorubicin hydrochloride liposome injection in patients with platinum-resistant relapsed intermediate to advanced epithelial ovarian cancer, and to provide a basis for recommending the SG001 combination dosing regimen for subsequent studies. This study will enroll patients with histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer, FIGO stage II-IV, platinum-resistant relapse (defined as disease progression within 6 months after the last platinum-containing chemotherapy) and non-platinum refractory (defined as disease progression within 4 weeks after the first platinum-containing chemotherapy) with up to three prior lines of platinum-containing systemic chemotherapy, up to two lines of platinum-free systemic chemotherapy, and at least one measurable tumor lesion (according to RECIST 1.1).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female patients aged 18-75 (inclusive) years old (based on the day of signing the informed consent).
- •Histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal, FIGO stage II-IV (per FIGO 2014).
- •Patients with platinum-resistant relapse (defined as disease progression within 6 months after the last platinum-containing chemotherapy) and non-platinum refractory (defined as disease progression within 4 weeks after the first platinum-containing chemotherapy). Previously received up to three lines of platinum-containing system chemotherapy and up to two lines of platinum-free system chemotherapy.
- •Patients must provide sufficient qualified FFPE tumor tissue specimens or sections for PD-L1 detection.
- •At least one measurable lesion per RECIST 1.1 at baseline. Measurable lesions should not have received local treatment such as radiotherapy (lesions located within previous radiotherapy areas may also be selected as a target lesion if progression is confirmed).
- •Eastern Cooperative Oncology Group (ECOG) physical status score: 0 or
- •Life expectancy ≥3 months.
- •Vital organ function meets the following requirements (no blood transfusion, no use of hematopoietic stimulating factor, and no use of medication to correct blood cell count within 14 days prior to first administration):
- •A) Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L; B) Platelet count (PLT) ≥ 75×10\^9/L; C) Hemoglobin (HGB) ≥ 9 g/dL; D) Serum creatinine Cr ≤ 1.5×ULN or creatinine clearance Ccr ≥ 50 mL/min; E) Total bilirubin (TBil) ≤ 1.5×ULN (3×ULN for patients with Gilbert's syndrome); F) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN (≤ 5×ULN for patients with liver metastasis); G) Activated partial thromboplastin time (APTT) and international standardized ratio (INR) ≤ 1.5×ULN (no correction with anticoagulants or other drug affecting coagulation function within 14 days before the first administration, except long-term anticoagulant therapy is needed.).
- •Toxic and side effects caused by previous anti-tumor therapy should be restored to ≤1 grade (CTCAE 5.0) (except residual alopecia and fatigue) before enrollment.
Exclusion Criteria
- •A history of severe allergic reaction and uncontrolled allergic asthma to monoclonal antibody preparations.
- •Untreated known CNS metastases, or treated CNS metastases but still with symptoms (except for residual signs or symptoms related to CNS treatment, and those with stable or improved neurological symptoms for at least 2 weeks prior to screening can be enrolled).
- •Patients with a history of primary immunodeficiency.
- •Patients with an active autoimmune disease or a history of autoimmune disease, but with well-controlled type Ⅰ diabetes, well-controlled hypothyroidism requiring only hormone replacement therapy, skin conditions that do not require general treatment (such as vitiligo, psoriasis, or alopecia), or patients whose disease is not expected to recur in the absence of external triggers, will be screened for further enrollment.
- •Baseline cardiac ejection fraction is less than 50% or the lower limit of normal; history of clinically significant prolonged QTc interval (\> 450 ms in male, \> 470 ms in female); cardiac lesions caused by previous use of anthracyclines; serious cardiovascular disease, such as New York Heart Association (NYHA) grade 2 or higher heart failure, previous myocardial infarction within 3 months, poorly controlled arrhythmias, or unstable angina.
- •Severe arterial/venous thrombosis events (such as transient ischemic attack, cerebral haemorrhage, cerebral infarction, deep venous thrombosis, pulmonary embolism, etc.) within 3 months prior to screening.
- •Previous interstitial lung disease (except local interstitial pneumonia induced by radiotherapy), non-infectious pneumonia requiring glucocorticoid therapy.
- •Have received any other antibodies/drugs that act on T cell co-stimulation or checkpoint pathways (including PD-1, PD-L1, PD-L2, CTLA-4, OX40, C137 inhibitors, etc.).
- •Patients with immune related AE CTCAE 5.0 grade score ≥ 3 after receiving immunotherapy.
- •Major surgery or radical radiotherapy within 28 days prior to the first administration, or palliative radiotherapy within 14 days prior to the first administration, or radiation agents (strontium, samarium, etc.) within 56 days prior to the first administration.
Arms & Interventions
Group A: SG001 + doxorubicin hydrochloride liposome injection
Two-thirds of the patients will be randomly assigned to group A to receive SG001 240 mg, IV, every 2 weeks (1 cycle every 4 weeks), and doxorubicin hydrochloride liposome injection 40 mg/m\^2, IV, every 4 weeks (1 cycle).
Intervention: SG001
Group A: SG001 + doxorubicin hydrochloride liposome injection
Two-thirds of the patients will be randomly assigned to group A to receive SG001 240 mg, IV, every 2 weeks (1 cycle every 4 weeks), and doxorubicin hydrochloride liposome injection 40 mg/m\^2, IV, every 4 weeks (1 cycle).
Intervention: Doxorubicin hydrochloride liposome injection
Group B: doxorubicin hydrochloride liposome injection
One-third of the patients will be randomly assigned to group B to receive doxorubicin hydrochloride liposome injection 40 mg/m\^2, IV, every 4 weeks (1 cycle).
Intervention: Doxorubicin hydrochloride liposome injection
Outcomes
Primary Outcomes
1. Objective response rate (ORR, assessed by investigators according to RECIST 1.1 criteria)
Time Frame: From date of first drug administration until the first documented progression of disease, patient withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest.
ORR is defined as the proportion of all patients with a best evaluation of complete response or partial response (according to RECIST version 1.1 criteria), from the date of administration to the date of patients' withdrawal or study completion or termination.
Secondary Outcomes
- Overall survival (OS)(From date of first drug administration until the first documented progression of disease, patient withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest,up to 3years..)
- Progression-free survival (PFS)(From date of first drug administration until the first documented progression of disease, patient withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest,up to 3 years.)
- Disease control rate (DCR)(From date of first drug administration until the first documented progression of disease, patient withdrawal, lose to follow-up, death, initiating a subsequent cancer therapy, or study completion or termination, whichever occurs earliest,up to 2 years.)
- Treatment emergent adverse event (TEAEs)(From the date of signing Informed Consent Form (ICF) up to 28 days following the last dose of study drug, immune related adverse events will be recorded until 90 days after the last dose.)