SHR-1210 in Combination With Apatinib in Patients With Metastatic, Persistent, or Recurrent Cervical Cancer

Phase 2

Completed

• Conditions: Recurrent Cervical Carcinoma; Metastatic Cervical Cancer
• Interventions: Drug: SHR-1210; Drug: Apatinib

• Registration Number: NCT03816553
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The purpose of this study is to explore the efficacy and safety of SHR-1210 in combination with apatinib in treating patients with metastatic, persistent, or recurrent cervical cancer.

Detailed Description

SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1). Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) selectively inhibits Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2). Patients with metastatic, persistent, or recurrent cervical cancer who failed to first-line chemotherapy +/- bevacizumab will received SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks and apatinib 250mg orally once daily. The efficacy and safety will be observed.

Study Timeline

• Study First Submitted: 2019-01-13
• Study Start: 2019-01-19
• Study First Submitted QC: 2019-01-24
• Study First Posted: 2019-01-25
• Primary Completion: 2020-04-30
• Study Completion: 2022-08-31
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-08
• Last Update Posted: 2023-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 45

Inclusion Criteria

1. Patients must have metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy;

2. Age ≥ 18 years and ≤ 70 years;

3. Patients must have measurable disease per RECIST 1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI),; a lymph node must be ≥ 15 mm in short axis. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

5. Life expectancy exceeds 3 months;

6. Patients must have had at least one prior systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix.

   Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix; adjuvant therapy includes cisplatin given concurrent with primary radiation therapy (CCRT) and adjuvant chemotherapy given following the completion of concurrent chemotherapy and radiation therapy

7. Patients must have adequate organ function

   • Absolute neutrophil count (ANC) ≥ 1.5×10^9/L
   • Platelet count ≥ 80 × 10^9/L
   • Hemoglobin ≥ 90 g/L
   • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
   • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 × ULN may be enrolled)
   • Creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula)
   • Baseline albumin ≥ 28 g/L
   • Thyroid-stimulating hormone (TSH) levels ≤ 1 × ULN (however, patients with free Triiodothyronine [FT3] or free Thyroxine [FT4] levels ≤ 1 × ULN may be enrolled)

8. Written informed consent.

Exclusion Criteria

1. Histopathologic diagnoses of tumors other than squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma.
2. Participated in other clinical trials, or finish other clinical trials within 4 weeks.
3. Prior exposure to immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 antibodies, or prior exposure to apatinib.
4. Known history of hypersensitivity to any components of the SHR-1210 formulation, or other monoclonal antibody.
5. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
6. Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
7. Clinically significant cardiovascular diseases, including but not limited to congestive heart failure (New York heart association (NYHA) class > 2), unstable or severe angina, severe acute myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.
8. Arterial thrombus or phlebothrombosis within 6 months.
9. Hypertension that can not be well controlled through antihypertensive drugs (systolic pressure ≥ 140 mm Hg and/or diastolic pressure ≥ 90 mm Hg)
10. Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
11. Coagulation abnormalities (INR>2.0、PT>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
12. Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events (except for alopecia) due to a previously administered agent.
13. Has known active central nervous system metastases.
14. Patients with a prior invasive malignancy who have had any evidence of disease within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
15. Has an active infection requiring systemic therapy.
16. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
17. Hepatitis B virus (HBV) >2000 IU/ml or DNA ≥ 1×10^4/ml; or hepatitis C virus (HCV) RNA ≥ 1×10^3/ml).
18. Has received a live vaccine within 4 weeks prior to the first dose of trial treatment. Note: Injection of inactivated viral vaccines against seasonal influenza are allowed.
19. Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SHR-1210 + Apatinib	SHR-1210	Participants receive SHR-1210 200mg (3mg/kg for underweight patients) intravenously every 2 weeks and apatinib 250mg orally once daily until disease progression or unacceptable toxicity
SHR-1210 + Apatinib	Apatinib	Participants receive SHR-1210 200mg (3mg/kg for underweight patients) intravenously every 2 weeks and apatinib 250mg orally once daily until disease progression or unacceptable toxicity

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 12 months	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Up to approximately 24 months	Progression-free survival is defined as the duration from date of enrollment to the first occurrence of progression of disease or death from any cause
Overall survival (OS)	Up to approximately 24 months	Overall survival is defined as the duration from date of enrollment to the date of death from any cause.
6-month PFS rate	From date of enrollment up to 6 months	The rate of 6-month PFS
Duration of Response (DCR)	Up to approximately 24 months	DCR is defined as the percentage of participants in the analysis population who have a CR, PR or stable disease (SD) per RECIST 1.1.
Duration of Response (DOR)	Up to approximately 24 months	DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
9-month OS rate	From date of enrollment up to 9 months	The rate of 9-month OS
Incidence of Adverse Events (AEs) in the treatment of SHR1210 in combination with apatinib	Up to approximately 24 months	Number of participants with adverse events occurring up to 30 days after the last administration are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.

Trial Locations

Locations (3)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China

The First affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guanzhou, Guangdong, China

Guangzhou Panyu Central Hospital; 🇨🇳 Guangzhou, Guangdong, China