A Single Arm, Open Label, Phase 1b Study of Xevinapant in Combination With Weekly Cisplatin and Intensity-modulated Radiotherapy to Assess Safety and Tolerability in Participants With LA SCCHN, Suitable for Definitive Chemoradiotherapy (HyperlynX)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 23
- 主要终点
- Number of Participants With Dose Limiting Toxicity (DLT)-Like Events
研究概览
简要总结
The purpose of this study is to evaluate the tolerability and safety of Xevinapant when added to weekly cisplatin-based concurrent chemoradiotherapy (CRT) in the treatment of participants with unresectable locally advanced squamous cell carcinoma of the head and neck, suitable for definitive chemoradiotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants having an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 - 1
- •Histologically confirmed diagnosis in previously untreated Locally Advanced Squamous Cell Carcinoma of Head and neck (LA SCCHN) patient (Stage III, IVA, or IVB according to the American Joint Committee on Cancer [AJCC]/ Tumor Nodes and metastases (TNM) Staging System, 8th Edition) suitable for definitive Chemoradiotherapy (CRT), with one of the following primary sites: oropharynx (OPC) Human Papillomavirus (HPV)-negative, hypopharynx, and larynx
- •Participant should be able to swallow liquids or has an adequately functioning feeding tube, gastrostomy, or jejunostomy in place. For participants requiring liquid nutrition at baseline or during the study including the follow-up period, access to liquid nutrition supply should be ensured
- •Participant with evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by CT scan and/or MRI, based on RECIST v 1.
- •Adequate hematological, hepatic, and renal function as defined in the protocol
- •Other protocol defined inclusion criteria could apply
排除标准
- •Primary tumor of nasopharyngeal, paranasal sinuses, nasal, or oral cavity, salivary, thyroid, or parathyroid gland pathologies, skin, or unknown primary site
- •Metastatic disease (Stage IVC as per AJCC/TNM, 8th Edition)
- •Existing need of a hearing aid or greater than or equal to (>=) 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated
- •Known history of infection with human immunodeficiency virus (HIV). If unknown history of HIV, an HIV screening test is to be performed and participants with positive serology for HIV-1/2 must be excluded
- •Known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery in the last 12 months that may limit oral absorption
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Xevinapant + Cisplatin + IMRT
Participants will receive xevinapant once daily from Day 1 to Day 14, per 3-week cycle (Each cycle is of 3 weeks). The first three cycles are given in combination with weekly cisplatin and radiotherapy, followed by 3 cycles of monotherapy xevinapant.
干预措施: Xevinapant (Drug)
Xevinapant + Cisplatin + IMRT
Participants will receive xevinapant once daily from Day 1 to Day 14, per 3-week cycle (Each cycle is of 3 weeks). The first three cycles are given in combination with weekly cisplatin and radiotherapy, followed by 3 cycles of monotherapy xevinapant.
干预措施: Cisplatin (Drug)
Xevinapant + Cisplatin + IMRT
Participants will receive xevinapant once daily from Day 1 to Day 14, per 3-week cycle (Each cycle is of 3 weeks). The first three cycles are given in combination with weekly cisplatin and radiotherapy, followed by 3 cycles of monotherapy xevinapant.
干预措施: intensity-modulated radiation therapy (IMRT) (Radiation)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicity (DLT)-Like Events
时间窗: Time from the first dose of study intervention day upto 35 days (5 weeks)
DLT-like events defined as any of the following treatment-related adverse events (AEs) or lab abnormalities occurring during the 5-week DLT-like assessment period and assessed as related to the study intervention: Grade 4 asymptomatic neutropenia more than (\>) 7 days; Grade 2-3 febrile neutropenia; Grade 4 thrombocytopenia without bleeding more than and equal to (\>=) 5 days or Grade 2-3 with bleeding or requiring transfusion; Grade 2-3 nonhematologic toxicity (e.g., renal impairment based on eGFR, Grade 4 skin toxicity/mucositis interfering with treatment); less than (\<) 60% planned cumulative dose of xevinapant or cisplatin due to AE; \>2-week Radiation therapy (RT) delay due to AE; Grade \>=2 ototoxicity worsening \>=2 grades from baseline and considered treatment-limiting; Hy's Law DILI; Grade \>=3 lab abnormalities; any life-threatening or Grade 5 toxicity.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs(Screening up to end of treatment (Day 134) and then follow up every 3 months (assessed up to maximum 6 months))
- Absolute Estimated Glomerular Filtration Rate (eGFR) Values(At Cycle1 Day 4 (C1D4), C1D11, C1D18, C2D1, C2D4, C2D11, C2D18, C3D1, C3D4, C4D1, C5D1, C6D1 and End of treatment (Day 134) (each cycle is of 3 weeks))
- Absolute Change From Baseline in eGFR(Baseline, C1D4, C1D11, C1D18, C2D1, C2D4, C2D11, C2D18, C3D1, C3D4, C4D1, C5D1, C6D1 and End of treatment (Day 134) (each cycle is of 3 weeks))
- Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 Criteria as Assessed by Investigator(Up to approximately 6 months)
- Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria as Assessed by Investigator(Time from randomization to the first documented disease progression, or death due to any cause, whichever occurs first (up to approximately 6 months))
- Locoregional Control (LRC) According to RECIST Version 1.1 Criteria As Assessed by Investigator(Time from date of the first treatment until date of the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes or End of Study, assessed approximately up to 6 months)
- Time to Subsequent Systemic Cancer Treatments(Time from date of the first treatment administration until the start date of the first subsequent systemic cancer treatment for SCCHN or End of study, assessed up to approximately 6 months)