Cervical Cancer
Conditions
Brief summary
This study is a single-arm, multicenter, Phase II study to evaluate the efficacy and safety of the treatment of Serplulimab plus Bevacizumab in combination with chemotherapy in 1L treatment of patients with untreated recurrent or metastatic cervical cancer. Approximately 48 eligible subjects are planned to be enrolled across all sites. The dosing regimen is: Serplulimab plus Bevacizumab combined with chemotherapy (cisplatin, paclitaxel). Each cycle is 21 days (every 3 weeks). Subjects will receive Cisplatin plus Paclitaxel up to 4-6 cycles. The maximum duration of treatment with Serplulimab is 2 years (up to 35 cycles). During the study treatment period, the subjects will receive imaging examination and response assessments every 6 weeks (± 7 days) in the first 48 weeks, every 9 weeks (± 7 days) in 48-96 weeks, and then every 12 weeks (± 7 days). After the treatment discontinuation visit, the subjects will enter the safety follow-up period and survival follow-up period.
Interventions
DRUGSerplulimab
Recombinant anti-PD-1 humanized monoclonal antibody injection
DRUGBevacizumab
Humanized anti-VEGF monoclonal antibody injection
Sponsors
Sichuan Cancer Hospital and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed Informed Consent Form (ICF) 2. Women, age ≥ 18 years and ≤ 75 years at time of signing ICF 3. Histologically or cytologically confirmed cervical cancer (pathological types: squamous cell carcinoma, adenocarcinoma \[except mucinous adenocarcinoma\], adenosquamous carcinoma) 4. Recurrent, progressive, or metastatic cervical cancer that is not amenable to surgery or radiotherapy/chemoradiotherapy (other than palliative radiotherapy to bone lesions). Recurrent and metastatic lesions should provide cytological and/or pathological biopsy evidence of cervical cancer metastasis as far as possible. 5. No systemic anti-tumor treatment for this recurrent, progressive or metastatic tumor. Note: a. Patients with initially diagnosed stage IVb disease should not have received systemic anti-tumor treatment; b. For patients previously treated with platinum-based first-line (neoadjuvant) adjuvant chemotherapy/radical chemoradiotherapy, the time from the last chemotherapy to disease recurrence is \> 6 months; c. Patients treated with radiotherapy/concurrent chemoradiotherapy (only receiving platinum-based sensitization) can be enrolled after the completion of radiotherapy if they relapse outside the radiation field. If there is recurrence within the radiation field (RECIST 1.1 is met) and the target lesion is located in the radiation field, the patient can be enrolled more than 3 months after the completion of radiotherapy; d. For patients who have not received previous chemoradiotherapy, if chemoradiotherapy is required first (only platinum single agent sensitization is received), the patient can be enrolled more than 3 weeks after the completion of radiotherapy. 6. Prior anticancer TCM therapy must have ended ≥ 7 days prior to first study treatment (Cycle 1, Day 1) and all antineoplastic treatment-related AEs must have recovered to ≤ Grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0 (except Grade 2 alopecia). 7. At least one measurable target lesion as assessed by the investigator per RECIST 1.1 within 4 weeks prior to enrollment. Note: Measurable target lesions should not have received local therapy such as radiotherapy (for lesions located in previously irradiated areas, target lesions can also be selected in case of definite progression \[according to RECIST 1.1\]). 8. ECOG PS score of 0 or 1 within 7 days prior to enrollment. 9. Expected survival ≥ 12 weeks. 10. Hepatitis B surface antigen (HBsAg) (-) and hepatitis B core antibody (HBcAb) (-). Hepatitis B virus deoxyribonucleic acid (HBV-DNA) \< 2500 copies/mL or 500 IU/mL if HBsAg (+) or HBcAb (+). 11. Subjects who are HCV antibody (-) or HCV-RNA negative may be enrolled; if HCV-RNA is positive, subjects must have alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 3 × ULN to be enrolled. Subjects with co-infection with hepatitis B and C are excluded (positive test for HBsAg or HBcAb and positive test for HCV antibody). 12. Adequate major organ function as defined by the following criteria (no transfusions, albumin, recombinant human thrombopoietin, or colony-stimulating factor \[CSF\] within 14 days prior to enrollment in this study): Hematological system Neutrophils (ANC) 1.5 x 109/L Platelets (PLT) 100 x 109/L Hemoglobin (Hb) 90 g/L Hepatic function Total bilirubin (TB) ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤ 2.5 × ULN; * 5 × ULN for patients with liver metastases; Aspartate aminotransferase (AST) ≤ 2.5 × ULN; * 5 × ULN for patients with liver metastases; Albumin ≥ 30 g/L Renal function Serum creatinine (Cr) ≤ 1.5 × ULN; Creatinine clearance ≥ 60 mL/min if \> 1.5 × ULN (calculated according to Cockcroft-Gault formula) Coagulation function Activated partial thromboplastin time (APTT) ≤ 1.5 x ULN Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x ULN 13. Female patients must meet: i. Menopause (defined as no menses for at least 1 year and no other confirmed cause other than menopause), or ii. Have been surgically sterilized (removal of ovaries and/or uterus), or iii. Childbearing potential, but must meet: * Must have a negative serum pregnancy test within 7 days prior to randomization, and * Agree to practice contraception with an annual failure rate of \< 1% or remain abstinent (refrain from heterosexual intercourse) (from signing the ICF to at least 6 months after the last dose of investigational drug and at least 6 months after the last dose of chemotherapeutic drugs) (methods of contraception with an annual failure rate of \< 1% include bilateral tubal ligation, male sterilization, correct use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper-containing intrauterine devices or condoms), AND * Do not breastfeed.
Exclusion criteria
Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 2 years | Defined as the proportion of patients whose best overall response is a partial response (PR) or a CR during the study, as determined by investigators |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Up to approximately 2 years | Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD) |
| Progression Free Survival (PFS) | Up to approximately 2 years | Defined as the time from enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by investigators |
| Duration of Response (DOR) | Up to approximately 2 years | Defined as the time from the first occurrence of a documented objective response (CR or PR) to disease progression, or death from any cause, whichever occurs first |
| 3-year Overall Survival (OS) | Up to approximately 2 years | Defined as the time from enrollment to death, regardless of cause of death. For subjects who had not been reported to have died at the time of analysis, the date they were last known to be alive was used as the censoring date for OS |
| Number of Participants Who Experience One or More Adverse Events (AEs) | From randomization through 30 days after last dose of study treatment (Up to approximately 25 months) | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
Countries
China
Contacts
Primary ContactGuonan Zhang
Backup ContactHong Liu
Outcome results
None listed