Status and phase
Conditions
Treatments
About
This is an open-label, multicenter, Phase II clinical study to evaluate the efficacy and safety of SKB518 as monotherapy or combination therapy in patients with advanced gynecological malignancies.
This study will include 5 cohorts: SKB518 as monotherapy in advanced ovarian cancer; SKB518 as monotherapy in advanced cervical cancer and endometrial cancer; SKB518 in combination with Carboplatin in advanced ovarian cancer; SKB518 in combination with Carboplatin and Bevacizumab in advanced ovarian cancer; and SKB518 in combination with Bevacizumab in advanced ovarian cancer.
Study hypothesis: SKB518 will show meaningful clinical activity and a favorable risk benefit profile in gynecological malignancies.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Provide signed written informed consent and demonstrate understanding of and agreement to comply with study requirements and the study visit schedule.
Age
Be ≥ 18 years and ≤ 75 years of age at the time of informed consent signing.
Participant Type and Disease Characteristics
Have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 within 2 weeks prior to first dose administration.
Have a cytologically or histologically confirmed gynecologic malignancy.
Participants in Cohorts A, C, D, and E with known breast cancer susceptibility gene (BRCA) mutations must have received poly(ADP-ribose) polymerase (PARP) inhibitor therapy, unless contraindicated.
Note:
PSOC is defined as radiographic progression/recurrence occurring ≥6 months after the last platinum-containing chemotherapy, i.e., the interval from the date of the last platinum therapy to radiographic evidence of disease progression per RECIST v1.1 should be ≥6 months (182 days).
Line counting rules for OC are as follows:
Provide approximately 10-13 unstained consecutive tumor tissue slides during the screening period for gene expression level testing (preferably from recently obtained tissue). If fresh tumor tissue samples are unavailable, archived tumor tissue samples obtained within 2 years prior to first study dose administration may be provided. If a participant is unable to provide archived tumor tissue samples within 2 years prior to first dose, or unable to provide a sufficient number of unstained consecutive tumor tissue slides, the investigator must discuss with the medical monitor to determine whether earlier obtained tumor tissue samples or a reduced number of slides may be accepted. Fine-needle aspiration biopsy specimens or core biopsies are insufficient for biomarker testing. Cell smears from centrifuged thoracic/abdominal/pelvic/pericardial effusion drainage, and bone lesions without soft tissue components or from decalcified bone tumor specimens are also unacceptable.
Have at least one target lesion per RECIST v1.1 criteria, accurately measured at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) (intravenous contrast preferred) with a longest diameter ≥10 mm (except for lymph nodes, which must have a short axis ≥15 mm), and the lesion must be suitable for repeated accurate measurement. Lesions located in previously irradiated areas or that have undergone biopsy may serve as measurable target lesions if there is documented evidence of disease progression per RECIST v1.1. Brain lesions are not considered target lesions.
Have an estimated life expectancy ≥12 weeks as assessed by the investigator.
Demonstrate adequate bone marrow, hepatic, renal, and coagulation function based on laboratory tests performed within 7 days prior to first dose (hematology tests required within 3 days prior to first dose) [supportive treatments, including transfusions, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), thrombopoietin (TPO), TPO receptor agonists (TPO-RA), and interleukins, are not permitted within 14 days prior to first dose]:
Have a left ventricular ejection fraction (LVEF) ≥50% by echocardiography (ECHO) within 28 days prior to first study drug administration.
Have recovered from all toxicities due to prior therapy (i.e., improved to Grade 0 or 1, or to levels specified in the eligibility criteria). Participants with unresolved, stable chronic (>3 months) toxicities not considered a safety risk (e.g., alopecia, hyperpigmentation, vitiligo) may be enrolled.
Gender and Contraceptive Requirements
Participants must agree to use highly effective contraception during study treatment.
Note: The reliability of abstinence as required in the eligibility criteria must be evaluated based on the duration of the clinical study and the participant's preferred and usual lifestyle. Periodic abstinence (e.g., calendar method, ovulation method, symptothermal method, or post-ovulation method) is not an acceptable contraceptive method.
Female participants eligible for study participation must be non-pregnant (see Appendix 3), non-lactating, and meet at least one of the following conditions:
Exclusion criteria
Participants meeting any of the following criteria will be excluded:
Prior/Current Study Experience
Participation in any other interventional clinical study, except for observational (non-interventional) studies or follow-up periods of interventional studies.
Disease Characteristics
For participants with ovarian cancer, mixed tumors containing sarcomatous components or borderline ovarian tumors.
- For participants in Cohorts C-E, mixed tumors containing high-grade serous carcinoma components and other components, or endometrioid, clear cell, mucinous, or sarcomatous histology, or mixed tumors containing any of the above histological types, or low-grade/borderline ovarian tumors.
Prior/Concomitant Therapy
Prior receipt of any of the following treatments:
a) Any drug therapy targeting topoisomerase I, including irinotecan, topotecan hydrochloride for injection, antibody-drug conjugates (ADCs) containing topoisomerase I, etc.
Receipt of other antineoplastic therapy within 4 weeks prior to first study drug administration, including systemic chemotherapy, targeted therapy, immunotherapy, intraperitoneal perfusion chemotherapy, tumor embolization, or interventional chemotherapy, etc. For oral PARP inhibitors and traditional Chinese medicines indicated for antineoplastic therapy, the washout period is 2 weeks or 5 half-lives, whichever is longer.
Receipt of strong cytochrome P450 (CYP3A4) inhibitors or inducers, or BCRP inhibitors (see Appendix 8) within 2 weeks prior to first dose or within 5 half-lives of the known drug, whichever is longer.
Receipt of live vaccine vaccination within 4 weeks prior to first study drug administration, or planned receipt of any live vaccine during the study.
Persistence of adverse reactions from prior antineoplastic therapy that have not resolved to Grade 0, Grade 1, or baseline status per NCI-CTCAE v5.0 criteria prior to first study drug administration. Participants with unresolved, stable chronic (>3 months) toxicities not considered a safety risk (e.g., alopecia, hyperpigmentation, vitiligo) may be enrolled.
Major surgery (craniotomy, thoracotomy, or laparotomy, and other surgical types considered "major" by the investigator, excluding needle biopsy) within 4 weeks prior to first study drug administration, or anticipated major surgery during the study, or presence of serious unhealed wounds, trauma, or ulcers, etc.
Note: Palliative local surgical treatment for isolated lesions is acceptable.
Palliative radiotherapy within 2 weeks prior to first drug administration, or definitive radiotherapy within 4 weeks prior to first drug administration.
Any condition requiring systemic corticosteroid therapy (dose >10 mg/day prednisolone or equivalent) or other immunosuppressive therapy within 14 days prior to first study drug administration. Participants receiving intranasal, inhaled, topical, or local glucocorticoid injections (e.g., intra-articular injections), or glucocorticoids as prophylaxis for hypersensitivity reactions may be enrolled.
Medical Conditions
Known symptomatic central nervous system (CNS) metastasis and/or spinal cord compression and/or carcinomatous meningitis, or history of leptomeningeal carcinomatosis. Participants with asymptomatic CNS metastases (no neurological symptoms, no corticosteroid treatment required, and all metastatic lesions ≤1.5 cm in diameter) or with brain metastases that have been treated and are stable may be considered for enrollment if all of the following criteria are met: (a) Measurable disease outside the CNS; (b) No midbrain, pons, cerebellum, meninges, medulla oblongata, or spinal cord metastases; (c) Stable condition for at least 4 weeks with no new or enlarging metastases (clearly documented by clinical evidence); (d) Discontinuation of corticosteroids or anticonvulsants at least 2 weeks prior to first study drug administration. CNS lesions should be monitored regularly during the study.
History of corticosteroid-treated pneumonitis, or history of other clinically significant pulmonary disease (e.g., interstitial lung disease, non-infectious pneumonia, or uncontrolled pulmonary disease such as pulmonary fibrosis, severe radiation pneumonitis, and acute lung injury), or participants with suspected such disease on imaging during screening; clinically significant pulmonary function impairment due to concurrent pulmonary disease, including but not limited to: any serious underlying pulmonary disease (e.g., severe asthma, severe chronic obstructive pulmonary disease, or restrictive lung disease), or any autoimmune disease, connective tissue disease, or inflammatory disease potentially involving the lungs (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.).
Presence of the following conditions:
Known hypersensitivity to study drug or any of its components [including polysorbate 80 (II)], or history of serious allergic reaction to other monoclonal antibodies; known history of platinum hypersensitivity for Cohort C; known history of platinum or bevacizumab hypersensitivity for Cohort D; known history of bevacizumab hypersensitivity for Cohort E; and hypersensitivity to both CT and MRI contrast agents, or inability to undergo contrast-enhanced CT and contrast-enhanced MRI for any reason.
History of immunodeficiency disorders, including congenital or acquired immunodeficiency diseases.
Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
Pregnant or lactating women.
Tumor History
Participants with known other malignancies progressing within the past 5 years or requiring active treatment. Exceptions include adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ with no evidence of disease recurrence.
Tumor invasion of surrounding vital organs or tissues (e.g., mediastinal great vessels, superior and inferior vena cava, pericardium, heart, trachea, esophagus, etc.) and/or risk of gastrointestinal, respiratory, or other fistulas due to any cause.
Other Exclusion Criteria
Presence of other acute or chronic diseases or laboratory abnormalities that may increase the risk of study participation or administration, or interfere with interpretation of study results; presence of neurological, psychiatric, or social conditions affecting trial compliance, significantly increasing the risk of adverse events, or affecting the participant's ability to provide written informed consent.
Acute or chronic diseases or laboratory abnormalities that the investigator judges unsuitable for study participation, or any condition that the investigator believes interferes with evaluation of study drug, participant safety, or interpretation of study results, or any other condition that the investigator believes makes the participant unsuitable for this study.
Primary purpose
Allocation
Interventional model
Masking
280 participants in 5 patient groups
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Central trial contact
Xiaoping Jin, PhD
Data sourced from clinicaltrials.gov
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