Efficacy and Safety of Scipibaimab Combined With Tislelizumab in the Treatment of Patients With Recurrent and Metastatic Nasopharyngeal Carcinoma Who Have Failed First-line Treatment: a Multicenter, Single-arm, Non-randomized, Open-label Phase II Clinical Study
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Objective response rate
Overview
Brief Summary
This study aims to explore the efficacy and safety of scipibaimab combined with tislelizumab in patients with recurrent or metastatic nasopharyngeal carcinoma who have progressed after first-line therapy.
Detailed Description
In the immunotherapy era, patients with recurrent/metastatic nasopharyngeal carcinoma who progress after both platinum-based chemotherapy and PD-1 blockade lack further standard options. IL-4Rα inhibition can overcome PD-1 resistance by re-activating CD8+ T cells; combining scipibaimab (anti-IL-4Rα) with tislelizumab (anti-PD-1) has shown additive activity without overlapping toxicity. This trial will assess the efficacy and safety of the combination in patients who have failed prior platinum and PD-1 therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1\. Histologically or cytologically confirmed with recurrent or metastatic nasopharyngeal carcinoma which is not amenable to curative treatment with surgery and/or radiation therapy.
- •2\. Age ≥ 18 years and ≤ 75 years, both genders.
- •3\. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or
- •4\. Life expectancy of at least 3 months.
- •5\. Have failed for first-line platinum-based chemotherapy.
- •6\. Have failed for prior treatment with PD-1 antagonists +/- chemotherapy.
- •7\. Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
- •8\. Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment) as determined by: Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L; Hemoglobin ≥ 9 g/dL; serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN), (for subjects with liver metastases, TBIL ≤3×ULN ; ALT and AST≤5×ULN); Creatinine ≤1.5×ULN or creatinine clearance rate≥50 ml/min (Cockcroft-Gault formula); serum 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); INR, APTT≤1.5 x ULN.
- •9\. All women with fertility potential must undergo a urine or serum pregnancy test during screening and the results are negative.
- •10\. Written informed consent.
Exclusion Criteria
- •1.Known history of hypersensitivity to any components of the Tislelizumab formulation, or other monoclonal antibody.
- •2.Prior therapy with any anti-interleukin-4 receptor α (IL-4Rα) monoclonal antibody, anti-IgE monoclonal antibody, or other monoclonal antibodies/biological agents.
- •3.There was a history of severe bleeding, and any bleeding events with a serious grade of 3 or more in CTCAE5.0 occurred within 4 weeks before screening.
- •4.Before treatment, MRI showed that the tumor may have invaded important blood vessels (such as enclosing the internal carotid artery / vein), nasopharyngeal necrosis, or researchers have determined that the tumor is highly likely to invade important blood vessels and cause fatal massive bleeding during treatment.
- •5.Patients with abnormal blood coagulation and bleeding tendency (14 days before signing informed consent: INR is within the normal range without anticoagulant); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues. On the premise that the INR \< 1.5, low-dose warfarin (1mg orally, once a day) or low-dose aspirin (daily dose not more than 100mg) is allowed for preventive purposes.
- •6.Arteriovenous thrombosis occurred within one year before screening, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by intravenous catheterization due to early chemotherapy) and pulmonary embolism.
- •7\. Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix.
- •8\. Join another clinical study at the same time, received any research drug within 4 weeks before the first administration of the drug.
- •9\. Patients with any active autoimmune disease or a documented history of autoimmune disease such as pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism;
- •10\. 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.
Arms & Interventions
Scipibaimab combined with Tislelizumab
Patients with recurrent or metastatic nasopharyngeal carcinoma who have progressed after first-line platinum-based chemotherapy plus PD-1 inhibition will receive scipibaimab 300 mg subcutaneous and tislelizumab 200 mg intravenous every 3 weeks until disease progression, unacceptable toxicity, or completion of 2-year treatment window.
Intervention: Tislelizumab (Drug)
Scipibaimab combined with Tislelizumab
Patients with recurrent or metastatic nasopharyngeal carcinoma who have progressed after first-line platinum-based chemotherapy plus PD-1 inhibition will receive scipibaimab 300 mg subcutaneous and tislelizumab 200 mg intravenous every 3 weeks until disease progression, unacceptable toxicity, or completion of 2-year treatment window.
Intervention: Scipibaimab (Drug)
Outcomes
Primary Outcomes
Objective response rate
Time Frame: 2 years
An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI)
Secondary Outcomes
- Disease control rate(2 years)
- Duration of response(2 years)
- Progression-free survival rate(2 years)
- Overall survival rate(2 years)
- Incidence rate of adverse events (AEs)(2 years)
Investigators
Hai-Qiang Mai,MD,PhD
Director of the Department of Nasopharyngeal Carcinoma
Sun Yat-sen University