A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study of Cemiplimab Versus the Combination of Cemiplimab With ISA101b in the Treatment of Subjects With HPV16-Positive Platin-Resistant Oropharyngeal Cancer (OPC)

ISA Therapeutics B.V.0 个研究点目标入组 164 人开始时间: 2018年9月24日最近更新: 2018年10月1日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: ISA Therapeutics B.V.
入组人数: 164

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1. Males and females, = 18 years of age.
•2. Sign and date an IRB/IEC-approved written informed consent form.
•3. Be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
•4. Diagnosed with histologically confirmed recurrent or metastatic HPV16 positive OPC, not amenable to any therapy with curative intent. Subjects with HPV16 positive squamous cell carcinoma (SCC) of occult primary site, presenting with lymph node(s) in the neck, are also eligible.
•5. HPV16 genotyping determined by a specified central reference laboratory with an established polymerase chain reaction (PCR)-based assay.
•6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
•7. Tumor progression or recurrence on or after platinum-containing chemotherapy for the treatment of primary metastatic or recurrent disease, or within 6 months of platinum containing chemotherapy administered as part of neo-adjuvant or adjuvant therapy.
•8. Measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension with a minimum size of 10 mm by computed tomography (CT) scan or magnetic resonance imaging (MRI) per RECIST 1.1 criteria. Indicator lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation, unless there is documented progression after therapy.
•9. Fresh tumor tissue must be provided for biomarker correlative studies unless the investigator determines that this could impose a significant risk to the subject after discussion with Medical Monitor.
•10. Prior curative radiation therapy must have been completed at least 8 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration.
•11. Screening laboratory values must meet the following criteria (using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) and should be obtained within 14 days prior to randomization:
•i) White blood cell count (WBC) = 2/mL
•ii) Absolute neutrophil count (ANC) = 1.5/mL
•iii) Platelets = 100 x103/µL
•iv) Hemoglobin = 9.0 g/dL
•v) Serum creatinine = 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl)> 40 mL/min
•vi) Hepatic function:
•a. Total bilirubin = 1.5 x ULN (if liver metastases = 3 x ULN). Subjects with Gilbert’s Disease and total bilirubin up to 3 x ULN may be eligible if total bilirubin < 3.0 mg/dL.
•b. Transaminases (ALT and AST) = 3 x ULN (or = 5.0 x ULN, if liver metastases)
•c. Alkaline phosphatase = 2.5 x ULN (or = 5.0 x ULN, if liver or bone metastases)
•Note for subjects with hepatic metastases: If transaminase levels (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) > 3 x but = 5 x ULN, total bilirubin must be = 1.5 x ULN. If total bilirubin > 1.5 x but = 3 x ULN, both transaminases (AST and ALT) must be = 3 x ULN.
•Note regarding drug induced liver failure (DiLi): According to Hy's Law of Drug Induced Liver Injury a drug causes hepatocellular injury, generally defined as an elevated ALT or AST by 3-fold or greater above the upper limit of normal, combined with an elevation of serum total bilirubin of greater than 2× the upper limit of normal, without findings of cholestasis (defined as serum alkaline phosphatase activity less than 2× the upper limit of normal).
•i) Calcium levels must be normalized and maintained within normal limits f

排除标准

•1. Subjects with known active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if these have been treated and there is no MRI (or CT scan where MRI is contraindicated) evidence of progression for at least 4 weeks after treatment is complete. Base of skull involvement without definitive evidence of dural or brain parenchymal involvement is acceptable. Subjects who require treatment with immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
•2. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
•3. History of other malignancy = 3 years prior to entry into this trial with the exception of basal cell or squamous cell skin carcinoma which were treated with local resection only, OR carcinoma in situ of the cervix, prostate or breast, OR low grade non-muscle invasive superficial bladder cancer (TaLG)/carcinoma in situ of the bladder.
•4. Subjects with active, known, diagnosed or suspected autoimmune disease. Subjects suffering from vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring thyroid hormone replacement therapy, or psoriasis not requiring systemic treatment can be enrolled.
•5. Patients diagnosed with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis or another condition requiring immunosuppressive doses of systemic medication such as systemic corticosteroids or absorbed topical corticosteroids (doses = 10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical corticosteroids and adrenal replacement doses < 10 mg daily prednisone or equivalent are permitted.
•6. Prior treatment with an anti-PD-1 antibody (e.g., nivolumab, pembrolizumab, cemiplimab), as well as anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
•7. Prior treatment with therapeutic anti-HPV vaccines including ISA101 or ISA101b. Subjects who have received a preventive HPV vaccine are allowed.
•8. Grade 1 or greater toxicities attributed to systemic prior anti-cancer therapy other than alopecia, fatigue (NCI CTCAE), radiation dermatitis, laboratory abnormalities that are not considered clinically significant by the treating physician, before administration of study drug. Subjects with residual grade 1 toxicities or toxicities attributed to systemic prior anticancer therapy that have become chronic and are not expected to resolve, such as neuropathy after platinum based therapy, can be included in this trial.
•9. Treatment with any chemotherapy, biological therapy for cancer, or investigational therapy within 28 days of first administration of study treatment.
•10. Administration of any live vaccine within 30 days before first dose of study drug.
•11. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus or
•hepatitis C virus, except for:
•?? Subjects with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells/mm3 either spontaneously or on a stable antiviral regimen) are permitte

研究者

发起方

ISA Therapeutics B.V.

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