A Single-Arm, Multicenter, Phase II Study to Evaluate the Efficacy and Safety of Serplulimab Plus Bevacizumab in Combination With Chemotherapy in 1L Treatment of Patients With Untreated Recurrent or Metastatic Cervical Cancer
Overview
- Phase
- Phase 2
- Intervention
- Serplulimab
- Conditions
- Cervical Cancer
- Sponsor
- Sichuan Cancer Hospital and Research Institute
- Enrollment
- 48
- Locations
- 4
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
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.
Investigators
Guonan Zhang
Director, Head of Gynecologic Oncology Center
Sichuan Cancer Hospital and Research Institute
Eligibility Criteria
Inclusion Criteria
- •Signed Informed Consent Form (ICF)
- •Women, age ≥ 18 years and ≤ 75 years at time of signing ICF
- •Histologically or cytologically confirmed cervical cancer (pathological types: squamous cell carcinoma, adenocarcinoma \[except mucinous adenocarcinoma\], adenosquamous carcinoma)
- •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.
- •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.
- •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).
- •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 \[according to RECIST 1.1\]).
- •ECOG PS score of 0 or 1 within 7 days prior to enrollment.
- •Expected survival ≥ 12 weeks.
Exclusion Criteria
- •Patients who meet any of the following exclusion criteria will not be enrolled in the study:
- •Other active malignancy within 2 years or concurrently. Cured localized tumors, such as cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer and breast carcinoma in situ, can be enrolled.
- •Patients who are scheduled for or have received prior organ or bone marrow transplantation.
- •Patients with uncontrolled pleural effusion, pericardial effusion or ascites.
- •Central nervous system (CNS) or leptomeningeal metastases confirmed by imaging studies or pathology.
- •Myocardial infarction within 6 months prior to enrollment, poorly controlled arrhythmia (including QTc interval ≥ 470 ms for females) (QTc interval calculated using Fridericia's formula).
- •Class III-IV cardiac dysfunction according to New York Heart Association (NYHA) criteria or echocardiography: left ventricular ejection fraction (LVEF) \< 50%.
- •Poorly controlled hypertension (defined as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg), previous hypertensive crisis or hypertensive encephalopathy.
- •Human immunodeficiency virus (HIV) infection.
- •Patients with active pulmonary tuberculosis.
Arms & Interventions
Serplulimab plus Bevacizumab Combined With Chemotherapy
Each cycle being 21 days, Cisplatin plus Paclitaxel up to 4-6 cycles, the maximum duration of treatment with Serplulimab is 2 years (up to 35 cycles). * Serplulimab, 300 mg IV, Day1 of each cycle * Bevacizumab, 7.5 mg/kg, IV, Day1 of each cycle * Cisplatin: 50 mg/m2, IV, Day1 of each cycle * Paclitaxel: 175 mg/m2, IV, Day1 of each cycle
Intervention: Serplulimab
Serplulimab plus Bevacizumab Combined With Chemotherapy
Each cycle being 21 days, Cisplatin plus Paclitaxel up to 4-6 cycles, the maximum duration of treatment with Serplulimab is 2 years (up to 35 cycles). * Serplulimab, 300 mg IV, Day1 of each cycle * Bevacizumab, 7.5 mg/kg, IV, Day1 of each cycle * Cisplatin: 50 mg/m2, IV, Day1 of each cycle * Paclitaxel: 175 mg/m2, IV, Day1 of each cycle
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: 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 Outcomes
- Progression Free Survival (PFS)(Up to approximately 2 years)
- Duration of Response (DOR)(Up to approximately 2 years)
- 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))
- Disease Control Rate (DCR)(Up to approximately 2 years)
- 3-year Overall Survival (OS)(Up to approximately 2 years)