A Single-arm, Open-label, Phase Ⅱ Clinical Trial of Anti-PD-1 Antibody SHR-1210 or Anti-PD-L1 Antibody SHR-1316 Combined With Apatinib Mesylate as a Second-line Treatment for Advanced Esophageal Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Apatinib+ SHR-1210（Camrelizumab）
- Conditions
- Esophageal Cancer
- Sponsor
- The First Affiliated Hospital of Zhengzhou University
- Enrollment
- 125
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to observe and evaluate the efficacy and safety of Anti-PD-1 antibody SHR-1210 or Anti-PD-L1 antibody SHR-1316 plus apatinib as second-line treatment of advanced esophageal squamous cell.
Detailed Description
The incidence of esophageal cancer is ranked seventh in the world, and the mortality rate ranks sixth in the world. At present, the first-line treatment of advanced esophageal cancer is mainly based on the combination of paclitaxel, cisplatin and fluorouracil. After the failure of first-line treatment, there is no standard second-line treatment. We designed a single-arm, open phase II clinical trial of anti-PD-1 antibody SHR-1210 or Anti-PD-L1 antibody SHR-1316 plus apatinib as second-line treatment of advanced esophageal squamous cell. The purpose of this study is to observe and evaluate the efficacy and safety of Anti-PD-1 antibody SHR-1210 or Anti-PD-L1 antibody SHR-1316 plus apatinib as second-line treatment of advanced esophageal squamous cell.
Investigators
Feng Wang
Doctor
The First Affiliated Hospital of Zhengzhou University
Eligibility Criteria
Inclusion Criteria
- •Aged 18-75 years, males or females;
- •Histologically or cytologically confirmed as ESCC, locally advanced and unresectable, with local recurrence (local lymph node metastases) or distant metastases;
- •Having progressed or being intolerant to first-line systemic chemotherapy (including chemotherapy based on cisplatin, taxol or fluorouracil) or chemotherapy combined with immunotherapy. Patients are also eligible if they progress after maintenance treatment following the first-line chemotherapy, or if patients with postoperative recurrence or metastasis progress after concurrent radiochemotherapy. As for the radical concurrent chemoradiotherapy, neoadjuvant/adjuvant treatment (chemotherapy or radiochemotherapy), if patients progress during the treatment or within six months after treatment, it is considered as a failure of first-line treatment;
- •The best overall response of first-line immunotherapy is CR, PR or SD, and PFS ≥ 3 months;
- •According to the Response Evaluation Criteria In Solid Tumour (RECIST 1.1), there is at least one measurable lesion, which has not received any local treatment, such as radiotherapy (if the lesion within the region of the previous radiotherapy is confirmed to progress and satisfies RECIST1.1, it can be also selected as the target lesion) ;
- •Tissue samples should be provided for biomarker analysis. The newly harvested tissues are preferred. If the newly harvested tissues are not available, 5-8 archival paraffin sections (5 um thick) can be provided;
- •ECOG: 0\~1;
- •Expected survival time ≥ 12 weeks;
- •Adequate function of major organs defined as:(1) Routine blood test: a. HB ≥ 90 g/L; b. ANC ≥ 1.5 × 109/L; c. PLT ≥ 80 × 109/L;(2) Biochemical test: a. ALB ≥ 30 g/L; b. ALT and AST ≤ 2.5 ULN; if there is no liver metastasis, ALT and AST ≤ 5 ULN; c. TBIL ≤ 1.5ULN; d. Plasma Cr ≤ 1.5 ULN or creatinine clearance rate (CCr) ≥ 60 mL/min;
- •Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%).
Exclusion Criteria
- •Patients who have any active autoimmune diseases or a past history of autoimmune diseases (including but not limited to the following: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, and hyperthyroidism; leukoderma. Subjects with fully remitted childhood asthma and no need for any intervention during adulthood can be included; those still having the need for bronchodilators for medical intervention cannot be included);
- •Patients who are currently on immunosuppressors or systemic hormone therapy for immunosuppressive purposes (dose \> 10 mg/day, prednisone or other hormones with equivalent efficacy), and continue taking them within 2 weeks before recruitment;
- •ESCC patients with active bleeding in primary lesions;
- •ESCC patients in whom the primary lesions are not surgically resected and are not shrunken in size after radiotherapy;
- •Patients who have received treatment with VEGFR inhibitors, such as sorafenib, sunitinib, and apatinib;
- •Any of the following conditions that will interfere with oral medications: unable to swallow, having received gastroenterostomy, chronic diarrhea and intestinal obstruction;
- •Brain metastasis or brain metastases that have disappeared in less than 3 months;
- •Patients who have any severe and/or uncontrolled diseases, including: poor blood pressure control (systolic pressure ≥ 150 mmHg or diastolic pressure ≥ 100 mmHg); having myocardial ischemia or myocardial infarction and arrhythmia of Grade 1 and above (including QT interval ≥ 480 ms) and cardiac insufficiency of Grade 1; active or uncontrollable severe infection; liver diseases, such as decompensated liver failure, active hepatitis B (HBV-DNA ≥ 104 copy number/mL or 2000 IU/mL) or hepatitis C (positive for anti-HCV antibodies, and HCV-RNA higher than the lower limit of detection with the analytical method); routine urine test indicates urine protein ≥++ and confirms that the 24-hour urinary protein quantification\>1.0 g;
- •Patients whose wounds or bone fractures remain unhealed for a long period of time;
- •Pneumorrhagia \> NCI-CTC AE Grade1 within four weeks before recruitment; bleeding at other positions \>NCI-CTC AE Grade 2 within four weeks before recruitment; having a bleeding tendency (eg., active peptic ulcer) or currently receiving thrombolytic or anticoagulant therapy, such as warfarin, heparin, or their analogs;
Arms & Interventions
CohortA：Apatinib+SHR-1210（Camrelizumab）
Apatinib+SHR-1210（Camrelizumab）for ESCC who progressed or were intolerant to first-line systemic chemotherapy
Intervention: Apatinib+ SHR-1210（Camrelizumab）
CohortB：Apatinib+SHR-1210（Camrelizumab）
Apatinib+SHR-1210（Camrelizumab）for ESCC who have failed prior immune checkpoint inhibitor therapies
Intervention: Apatinib+ SHR-1210（Camrelizumab）
CohortC：Apatinib+SHR-1316（Adebrelimab）
Apatinib+SHR-1316（Adebrelimab）for ESCC who have failed prior immune checkpoint inhibitor therapies
Intervention: Apatinib+ SHR-1316（Adebrelimab）
CohortD：SHR-1316（Adebrelimab）+SHR-A2009
SHR-1316 was administered intravenously, 1200mg, Q3W; SHR-A2009 8mg/kg, iv, Q3W, for ESCC who have failed prior immune checkpoint inhibitor therapies.
Intervention: SHR-1316（Adebrelimab）+SHR-A2009
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: up to 1 year
the proportion of patients with a confirmed complete response or partial response on two consecutive occasions≥4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Secondary Outcomes
- 6-, 9- and 12-month OS rates(up to 12 months)
- Disease Control Rate (DCR)(up to 1 year)
- Progression-free Survival (PFS)(up to 2 year)
- Duration of response（DOR）(up to 2 year)
- Time to response（TTP）(up to 1 year)
- Overall survival(OS)(up to 2 year)
- 3- and 6-month PFS rates(up to 6 months)
- adverse events(Safety)(up to 2 years)