A Phase 2/3, Randomized Study of INBRX-106 Combined With Pembrolizumab Versus Pembrolizumab as First Line Treatment for Patients With Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) Expressing PD-L1 (CPS ≥20) (HexAgon-HN)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 410
- 试验地点
- 165
- 主要终点
- Phase 2: Objective Response Rate (ORR)
研究概览
简要总结
This seamless phase 2/3 randomized controlled study will evaluate the efficacy and safety of the hexavalent OX40 agonist antibody INBRX-106 combined with the anti-PD-1 antibody pembrolizumab versus pembrolizumab (+ placebo in phase 3) as first-line treatment for patients with locally advanced recurrent or metastatic head and neck squamous cell carcinoma (R/M HSNSCC) incurable by local therapies, expressing PD-L1 with a combined proportion score (CPS) ≥20.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Phase 2: open label; Phase 3: double-blind
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
- •Has histologically or cytologically confirmed diagnosis of metastatic, recurrent head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies.
- •Has tumor PD-L1 expression of CPS ≥
- •Tumor tissue must be provided for PD-L1 biomarker analysis.
- •Has human papilloma virus (HPV) testing results for oropharyngeal cancer by p16 immunohistochemistry (IHC) testing.
- •Has measurable disease per RECIST 1.1 guidelines.
- •Has the primary tumor location of the oral cavity, oropharynx, hypopharynx, or larynx.
- •Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Female patients of childbearing potential must have a negative highly sensitive pregnancy test within 72 hours prior to randomization and must not be breastfeeding.
- •Male and female patients of childbearing potential must be willing to completely abstain from heterosexual sex or agree to use a highly effective method of contraception.
排除标准
- •Has primary tumor site (any histology) of nasopharynx or salivary glands or occult primary site.
- •Has received prior systemic therapy (eg, prior chemo-, immune-, or biologic therapy) for locally advanced unresectable or metastatic HNSCC.
- •Prior systemic therapy completed >6 months prior to signing informed consent is allowed if given as part of multimodal treatment for locoregionally advanced disease with curative intent, and no PD/recurrence occurred within 6 months of its completion. Prior systemic immunotherapy in the locoregionally advanced disease with curative intent, including but not limited to anti-PD-(L)1 agents, is allowed if PD/recurrence occurred ≥12 months after its completion.
- •Has clinically active central nervous system metastases and/or carcinomatous meningitis.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- •Rapidly progressing disease or with features that may confer a high risk of tumor-associated hemorrhage or uncontrolled tumor pain.
- •Current or history of immune-related disease that required systemic treatment in past 2 years, except for replacement therapy.
研究组 & 干预措施
INBRX-106 plus pembrolizumab
Participants will receive INBRX-106 plus pembrolizumab, both given by intravenous (IV) infusion every 3 weeks (QW3)
干预措施: INBRX-106 (Drug)
pembrolizumab monotherapy (+ placebo in phase 3 part)
Participants will receive pembrolizumab (plus placebo in Phase 3), given by intravenous (IV) infusion every 3 weeks (QW3)
干预措施: INBRX-106 (Drug)
INBRX-106 plus pembrolizumab
Participants will receive INBRX-106 plus pembrolizumab, both given by intravenous (IV) infusion every 3 weeks (QW3)
干预措施: Pembrolizumab (Drug)
pembrolizumab monotherapy (+ placebo in phase 3 part)
Participants will receive pembrolizumab (plus placebo in Phase 3), given by intravenous (IV) infusion every 3 weeks (QW3)
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Phase 2: Objective Response Rate (ORR)
时间窗: up to 6 months
ORR is defined as the proportion of patients with a complete response (CR) or partial response (PR) on 2 consecutive occasions ≥4 weeks apart, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Phase 3: Progression-Free Survival (PFS)
时间窗: From randomization to first occurrence of progressive disease (PD) or death (up to 4 years)
PFS is defined as the time from randomization to first occurrence of PD, as determined by the Investigator according to RECIST v 1.1, or death from any cause (whichever occurs first).
Phase 3: Overall Survival (OS)
时间窗: From randomization until death from any cause (up to 4 years)
OS is the time from randomization to death due to any cause
次要结局
- TTCD in physical functioning (PF)(From randomization until treatment discontinuation (up to 2 years))
- Phase 3: Objective Response Rate (ORR)(From randomization until treatment discontinuation (up to 2 years))
- Duration of Response (DOR)(From the first occurrence of a documented objective response to PD or death (up to 4 years))
- Clinical Benefit Rate (CBR)(From randomization until treatment discontinuation (up to 2 years))
- TTCD in Global Health Status/quality of life (GHS/QoL)(From randomization until treatment discontinuation (up to 2 years))
- Incidence and severity of Adverse Events (AEs)(Up to approximately 24 months)
- Number of patients who experienced abnormalities in vital signs and clinical laboratory parameters(Up to approximately 24 months)
- Phase 3: Time to Chemotherapy (TTCtx)(From randomization until the start of chemotherapy or death (up to 4 years))
- Time to Confirmed Deterioration (TTCD) in Pain Presence and Interference(From randomization until treatment discontinuation (up to 2 years))
- TTCD in role functioning (RF)(From randomization until treatment discontinuation (up to 2 years))