A Phase 1, Open-Label, Multicenter Study to Assess Safety, Tolerability, Pharmacokinetics, and Efficacy of MK-4716 as Monotherapy and as Part of Combination Therapy in Participants With KRAS-Altered Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 21
- 主要终点
- Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLT)
研究概览
简要总结
Researchers are looking for new ways to treat certain advanced or metastatic solid tumors. The goal of this study is to learn about the safety of MK-4716 and if people tolerate it when taken alone or with other treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Subset of arm MK-4716 Dose Escalation and subset of arm MK-4716 + Cetuximab: Has a confirmed diagnosis of locally advanced unresectable or metastatic solid tumor
- •Subset of arm MK-4716 Dose Escalation and subset of arm MK-4716 + Cetuximab: Must demonstrate presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) alteration
- •Subset of arm MK-4716 Dose Escalation and subset of arm MK-4716 + Cetuximab: Has received at least 1 prior line of systemic therapy for locally advanced unresectable or metastatic disease
- •Arm MK-4716 + Pembrolizumab: Has a confirmed diagnosis of metastatic non-small cell lung cancer
- •Arm MK-4716 + Pembrolizumab: Must demonstrate presence of KRAS alteration
- •Arm MK-4716 + Pembrolizumab: Must be untreated
- •Has measurable disease
- •Has the ability to swallow and retain oral medication
排除标准
- •Arm MK-4716 + Pembrolizumab: Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
- •Arm MK-4716 + Pembrolizumab: Has received any prior immunotherapy and was discontinued from that treatment
- •Arm MK-4716 + Pembrolizumab: Has active autoimmune disease that has required systemic treatment in the past 2 years. Hormonal supplementation (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
- •History of human immunodeficiency virus infection
- •Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
- •Has a known active central nervous system metastases and/or carcinomatous meningitis
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Has active infection requiring systemic therapy
- •Has Hepatitis B or Hepatitis C virus infection
- •History of stem cell/solid organ transplant
- •Has not adequately recovered from major surgery or has ongoing surgical complications
研究组 & 干预措施
MK-4716 Dose Escalation
Participants receive MK-4716 at varying dose levels and schedules.
干预措施: MK-4716 (Drug)
MK-4716 + Pembrolizumab
Participants will receive MK-4716 + Pembrolizumab
干预措施: MK-4716 (Drug)
MK-4716 + Cetuximab
Participants will receive MK-4716 + Cetuximab
干预措施: MK-4716 (Drug)
MK-4716 + Pembrolizumab
Participants will receive MK-4716 + Pembrolizumab
干预措施: Pembrolizumab (Biological)
MK-4716 + Cetuximab
Participants will receive MK-4716 + Cetuximab
干预措施: Cetuximab (Biological)
结局指标
主要结局
Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLT)
时间窗: Up to approximately 28 days
A DLT is defined as the occurrence of protocol-specified toxicities, unless clearly related to disease progression or intercurrent illness.
Number of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 4 years
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Number of Participants Who Discontinue Study Intervention Due to an AE
时间窗: Up to approximately 4 years
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
次要结局
- Area Under the Concentration-Time Curve (AUC) of MK-4716(At designated timepoints (up to approximately 58 days))
- Maximum Plasma Concentration (Cmax) of MK-4716(At designated timepoints (up to approximately 58 days))
- Trough Plasma Concentration (Ctrough) of MK-4716(At designated timepoints (up to approximately 19 months))
- Half-Life (t1/2) of MK-4716(At designated timepoints (up to approximately 58 days))