A Phase II Study of Serplulimab Plus Bevacizumab in Combination With Chemotherapy in 1L Treatment of Untreated Recurrent or Metastatic Cervical Cancer

NCT05444374 | Unknown Phase 2

• 1 other identifier: HLX10IIT05
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

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.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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

  Up to approximately 2 years

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  Up to approximately 2 years

• Duration of Response (DOR)

  Up to approximately 2 years

• Disease Control Rate (DCR)

  Up to approximately 2 years

• 3-year Overall Survival (OS)

  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)

Study Arms (1)

Serplulimab plus Bevacizumab Combined With Chemotherapy

EXPERIMENTAL

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

Drug: Serplulimab; Drug: Bevacizumab

Interventions

Serplulimab DRUG

Recombinant anti-PD-1 humanized monoclonal antibody injection

Serplulimab plus Bevacizumab Combined With Chemotherapy

Bevacizumab DRUG

Humanized anti-VEGF monoclonal antibody injection

Serplulimab plus Bevacizumab Combined With Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 (+).
• 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).
• 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;
• × ULN for patients with liver metastases; Aspartate aminotransferase (AST) ≤ 2.5 × ULN;

You may not qualify if:

• 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.
• Patients with previous and current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, severely impaired pulmonary function, etc., which may interfere with the detection and management of suspected drug-related pulmonary toxicity.
• Patient has known active or suspected autoimmune disease. Patients with immune-related hypothyroidism on thyroid hormone replacement therapy and patients with well-controlled type I diabetes are allowed. Recovered Vitiligo or childhood asthma/allergies that do not require intervention or that do not require any intervention in adulthood are allowed.
• Treatment with a live vaccine within 28 days prior to enrollment. However, inactivated viral vaccines for seasonal influenza are allowed, but live attenuated influenza vaccines for intranasal use are not allowed.
• Patients requiring systemic corticosteroids (\> 10 mg/day prednisone efficacy dose) or other immunosuppressive medications within 14 days prior to enrollment or during the study. However, patients were permitted to use topical or inhaled corticosteroids and adrenal glucocorticoid replacement at doses ≤ 10 mg/day prednisone for efficacy in the absence of active autoimmune disease.
• Any active infection requiring systemic anti-infective therapy within 14 days prior to enrollment.
• Major surgery within 28 days prior to enrollment, this study Major surgery is defined as surgery that requires at least 3 weeks of recovery from surgery to be able to receive treatment for this study. Patients with tumor aspirate or lymph node harvest biopsy were allowed to enroll.

Sponsors & Collaborators

• Sichuan Cancer Hospital and Research Institute: lead

Study Sites (4)

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Location

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

Sicchuan Cancer Hospital

Chengdu, Sichuan, 610000, China

Location

Related Publications (5)

• Waggoner SE. Cervical cancer. Lancet. 2003 Jun 28;361(9376):2217-25. doi: 10.1016/S0140-6736(03)13778-6.

  PMID: 12842378 BACKGROUND

• Pfaendler KS, Tewari KS. Changing paradigms in the systemic treatment of advanced cervical cancer. Am J Obstet Gynecol. 2016 Jan;214(1):22-30. doi: 10.1016/j.ajog.2015.07.022. Epub 2015 Jul 26.

  PMID: 26212178 BACKGROUND

• Todo Y, Watari H. Concurrent chemoradiotherapy for cervical cancer: background including evidence-based data, pitfalls of the data, limitation of treatment in certain groups. Chin J Cancer Res. 2016 Apr;28(2):221-7. doi: 10.21147/j.issn.1000-9604.2016.02.10.

  PMID: 27199520 BACKGROUND

• Verma J, Monk BJ, Wolfson AH. New Strategies for Multimodality Therapy in Treating Locally Advanced Cervix Cancer. Semin Radiat Oncol. 2016 Oct;26(4):344-8. doi: 10.1016/j.semradonc.2016.05.003. Epub 2016 May 26.

  PMID: 27619255 BACKGROUND

• Moore DH, Blessing JA, McQuellon RP, Thaler HT, Cella D, Benda J, Miller DS, Olt G, King S, Boggess JF, Rocereto TF. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2004 Aug 1;22(15):3113-9. doi: 10.1200/JCO.2004.04.170.

  PMID: 15284262 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Guonan Zhang

  Sichuan Cancer Hospital and Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guonan Zhang

CONTACT

86-13881866599; zhanggn@hotmail.com

Hong Liu

CONTACT

86-13693447854; liuhaotian12@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of Gynecologic Oncology Center

Study Record Dates

• First Submitted: June 29, 2022
• First Posted: July 5, 2022
• Study Start: October 1, 2022
• Primary Completion: September 30, 2024
• Study Completion: December 31, 2025
• Last Updated: July 5, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)