An open-label Phase II randomized trial of BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first line therapy in patients with unresectable recurrent, or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) which is positive for human papilloma virus 16 (HPV16+) and expresses PD-L1. - AHEAD-MERIT

BioNTech SE0 个研究点目标入组 285 人开始时间: 2020年12月15日最近更新: 2024年1月15日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: BioNTech SE
入组人数: 285

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. Patients must sign the written ICF before any screening procedure. Informed consent must be documented before any trial-specific screening procedure is performed.
•2. Patients must be aged =18 years on the date of signing the informed consent.
•3. Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the trial.
•4. Patients who present histologically confirmed recurrent or metastatic HPV16+ HNSCC that is considered incurable by local therapies.
•5. Patients who have a tumor that expresses PD-L1 [CPS =1] as determined by the approved test PD-L1 IHC 22C3 pharmDx kit performed and evaluated according to the manufacturer's specifications and relevant regulatory approvals.
•6. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
•7. Patients must not have had prior systemic anticancer therapy administered in the incurable recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to randomization, if given as part of multimodal treatment for locally advanced disease is allowed.
•8. Patients who have measurable disease based on RECIST 1.1 as determined by the site and confirmed by blinded independent central review (BICR). Tumor lesions situated in a previously irradiated area are considered measurable, if progression has been demonstrated in such lesions by RECIST 1.1.
•9. Patients have Eastern Cooperative Oncology Group (ECOG) performance status =1.
•10. Patients have adequate bone marrow function as defined by hematological parameters described in the protocol.
•11. Patients have adequate hepatic function, as defined in the protocol.
•12. Patients should have adequate kidney function, assessed by the estimated glomerular filtration rate (eGFR) =30 mL/min/1.73m² using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation Kidney Disease Improving Global Outcomes [KDIGO] 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease; Levey et al. 2009).
•13. Patients should be stable with adequate coagulation, as determined by the investigator. Results should be discussed with the Medical Monitor if:
•a. international normalized ratio (INR) or prothrombin time (PT) >1.5 × ULN (unless on therapeutic anticoagulants with values within therapeutic window),
•b. activated partial thromboplastin time (aPTT) >1.5 × ULN (unless on therapeutic anticoagulants with values within therapeutic window).
•14. All patients must provide a tumor tissue sample (FFPE blocks or both slides and curls) from archival tissue, or fresh biopsy if a biopsy is performed as part of the patient's standard clinical practice before the first dose of trial treatment. The sample should be preferably derived from a current site of metastatic or recurrent disease. Otherwise, a sample from the primary tumor can be submitted. More information about sample quality, requirements, and handling will be provided in a laboratory manual.
•15. Women of childbearing potential (WOCBP) must have a negative serum (beta-human chorionic gonadotropin) at screening.
•16. WOCBP must agree to practice at least one highly effective method of contraception during trial, i.e., starting at screening, during the trial and for at least 6 months after receiving the last dose of BNT113 AND for at least 6 months after receiving the last dose of pembrolizumab.
•17. WOCBP must agree not to donate eggs (ova, oocytes) for the purp

排除标准

•1. Patients are pregnant or breastfeeding.
•2. Patients present primary tumor site of nasopharynx (any histology).
•3. Patients with uncontrolled intercurrent illness as defined in the protocol points a/b/c/d/e/f/ g/h/I/j/k/l/m.
•4. Patients with a known allergy, hypersensitivity, or intolerance to BNT113 or its excipients, or to pembrolizumab or its excipients.
•5. Patients who have had a splenectomy.
•6. Patients who have had major surgery (e.g., requiring general anesthesia) within 4 weeks before screening, or have not fully recovered from surgery, or have a surgery planned during the time of trial
•participation.
•7. Patients who have a known history (testing not required) or has a positive test at screening of any of the following:
•a. Human immunodeficiency virus (HIV) 1 or 2.
•b. Hepatitis B infection.
•c. Hepatitis C (unless considered cured).
•8. Patients with another primary malignancy that has not been in complete remission for at least 2 years, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, non-invasive basal or non-invasive squamous cell skin cancer, localized prostate cancer, non-invasive superficial bladder cancer or breast ductal carcinoma in situ).
•Note 1: Adjuvant hormone therapy used for breast cancer in long-term remission is allowed.
•Note 2: Any uncertainties should be discussed with the Medical Monitor.
•9. Patients with any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or
•confound the protocol-specified assessments.
•10. Patients who have received or currently receive the therapy/medication as defined in the protocol points a/b/c/d/e/f.
•11. Prior treatment with anti-cancer immunomodulating agents, such as blockers of PD 1, PD-L1, tumor necrosis factor receptor superfamily member 9 (TNFRSF9, 4 1BB, CD137), OX 40, therapeutic vaccines,
•cytokine treatments, or any investigational agent within 4 weeks or 5 half-lives of the agent (whichever is longer) before the first dose of BNT113.
•12.Treatment with non-systemic anti-cancer therapy (e.g., radiotherapy or surgery) within 2 weeks prior to randomization.
•Note: Prior treatment with bone resorptive therapy, such as bisphosphonates (e.g., pamidronate, zoledronic acid) and denosumab, is allowed.
•13. Current evidence of Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) Grade >1 toxicity before the start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in other eligibility criteria. Patients with Grade 2 neuropathy may be eligible at Investigator's discretion.
•14. Current evidence of new or growing brain or spinal metastases during screening. Patients with known brain or spinal metastases may be eligible if they:
•a. had radiotherapy or another appropriate therapy for the brain or
•spinal metastases,
•b. have no neurological symptoms (excluding Grade =2 neuropathy),
•c. have no evidence of clinical or radiological progression within 4 wks before signing the informed consent,
•d. do not require steroid therapy within 7 d before randomization or are undergoing slow steroid tapering, currently at doses =10 mg and neurologically stable.
•e. spinal bone metastases are allowed unless imminent fracture or cord
•compression is anticipated.
•15. Patients who have previously been enrolled in this trial (rescreening is allowed onc

研究者

发起方

BioNTech SE

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