A Phase 1/1b Open-label, Multicenter Clinical Study of MK-0472 as Monotherapy and Combination Therapy in Participants With Advanced/Metastatic Solid Tumors.
概览
- 阶段
- 1 期
- 干预措施
- MK-0472
- 疾病 / 适应症
- 未指定
- 发起方
- Merck Sharp & Dohme LLC
- 入组人数
- 178
- 试验地点
- 25
- 主要终点
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
The purpose of this study is to assess the efficacy, safety, and tolerability of MK-0472 administered as monotherapy and in combination with pembrolizumab (MK-3475) or MK-1084 in participants with histologically or cytologically confirmed diagnosis of advanced/metastatic solid tumors.
研究者
入排标准
入选标准
- •The main inclusion criteria include but are not limited to the following:
- •Has histologically or cytologically confirmed solid tumor by pathology report that is advanced/metastatic
- •Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to study enrollment
- •Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
- •Participants with human immunodeficiency virus (HIV) infection must have well controlled HIV on stable (\>4 weeks) antiretroviral therapy (ART)
- •Arm 1: Oncogenic receptor tyrosine kinase (RTK) pathway alterations confirmed by a historical report or local testing (tissue or blood) and have received, or been intolerant to, all available treatment known to confer clinical benefit
- •Arm 2: Tumor types known to be sensitive to anti-programmed cell death 1 protein (PD-1)/ligand 1 (L1) therapies are eligible. Tumor types permitted include: melanoma, non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/ROS1 mutations, renal cell carcinoma, urothelial carcinoma, Merkel cell carcinoma, MSI-high CRC, endometrial cancer, cervical cancer, small cell lung cancer, triple negative breast cancer, esophageal cancer, gastric cancer, biliary tract cancer, hepatocellular carcinoma, head and neck squamous cancer, cutaneous squamous cancer, anal squamous cancer, and mesothelioma
- •Arm 3: Has histologically OR blood-based confirmation of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has not recovered to common terminology criteria for adverse events (CTCAE) Grade 1 or better from any adverse events that were due to cancer therapeutics administered more than 4 weeks earlier. Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study
- •Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- •History of hyperparathyroidism or hypercalcemia
- •Has one or more of the following ophthalmological findings/conditions: a) Intraocular pressure \>21 mm Hg and/or any diagnosis of glaucoma b) Diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion and c) Diagnosis of retinal degenerative disease
- •Has clinically significant cardiovascular disease
- •Bullous exfoliative skin disorders of any grade
- •Known hypersensitivity to MK-0472, MK-1084, or pembrolizumab, or any of their excipients
- •Received therapy with a proton-pump inhibitor or an H2 histamine blocker receptor antagonist within 7 days before the first scheduled day of study dosing
- •Has discontinued prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor due to an adverse event
研究组 & 干预措施
MK-0472
Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens until disease progression or withdrawal/discontinuation.
干预措施: MK-0472
MK-0472 + Pembrolizumab
Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens until disease progression or withdrawal/discontinuation, plus pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: MK-0472
MK-0472 + Pembrolizumab
Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens until disease progression or withdrawal/discontinuation, plus pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: Pembrolizumab
MK-0472 + MK-1084
Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens, plus MK-1084 via oral capsule until disease progression or withdrawal/discontinuation.
干预措施: MK-0472
MK-0472 + MK-1084
Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens, plus MK-1084 via oral capsule until disease progression or withdrawal/discontinuation.
干预措施: MK-1084
结局指标
主要结局
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
时间窗: Up to approximately 56 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be reported.
Number of Participants Who Experience a Dose Limiting Toxicity (DLT) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
时间窗: At the end of Cycle 1 (each cycle is 21 days)
DLT will be defined as any drug-related AE observed during the DLT evaluation period (e.g. Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle.
Number of Participants Who Experience One or More Adverse Events (AEs)
时间窗: Up to approximately 56 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience one or more AE's will be reported.
次要结局
- Area Under the Concentration Time-curve From Time 0 to the End of the Dosing Period (AUCtau) of MK-0472(At predetermined timepoints predose and postdose up to Cycle 6 (Each cycle length = 21 Days))
- Lowest Plasma Concentration (Ctrough) of MK-0472(At predetermined timepoints Predose up to Cycle 6 (Each cycle length = 21 Days))
- Maximum Plasma Concentration (Cmax) of MK-0472(At predetermined timepoints postdose up to Cycle 6 (Each cycle length = 21 Days))