A Phase 1 Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 182
- 试验地点
- 18
- 主要终点
- Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to assess the safety and pharmacokinetics of boserolimab (MK-5890) when administered alone and in combination with pembrolizumab (MK-3475) in adults. Boserolimab monotherapy or boserolimab plus pembrolizumab combination therapy will be administered in adults with advanced solid tumors, including endometrial cancer, for up to 35 administrations (approximately 2 years). The safety and pharmacokinetics of boserolimab when administered with pembrolizumab, pemetrexed and carboplatin in adults with non-squamous non-small cell lung cancer (NSCLC) and boserolimab when administered with pembrolizumab and nab-paclitaxel in adults with triple-negative breast cancer (TNBC) will also be assessed.
详细描述
Participants receiving boserolimab monotherapy who experience disease progression may be eligible to switch to receiving boserolimab plus pembrolizumab combination therapy at an eligible dose for up to 35 cycles (approximately 2 years) at the discretion of the Investigator and approval of the Sponsor.
Per protocol, pharmacokinetic (PK) outcome measures will not be analyzed separately for the switch-over treatment arms.
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
- 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
- •Arms 1 & 2: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and has received or been intolerant to all treatment known to confer clinical benefit
- •Arm 3: Histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b per current American Joint Committee on Cancer criteria) non-squamous NSCLC
- •Arm 4: Triple-negative breast cancer (TNBC) that is locally recurrent, inoperable, not previously treated with chemotherapy, and which cannot be treated with curative intent OR metastatic disease not previously treated with chemotherapy
- •Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiologist. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- •Adequate organ function
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Male participants must agree to use adequate contraception during the treatment period and for at least 120 days after the last dose of boserolimab or pembrolizumab OR 180 days after the last dose of chemotherapeutic agents and refrain from donating sperm during this period
- •Female participants must not be pregnant or breastfeeding and agree to follow use adequate contraception during the treatment period and for at least 120 days after the last dose of boserolimab or pembrolizumab OR 180 days after the last dose of chemotherapeutic agents
- •Submit an evaluable baseline tumor sample for analysis (either a newly obtained or archival tumor sample)
排除标准
- •History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- •Clinically active central nervous system metastases and/or carcinomatous meningitis
- •Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb) and/or other components of the study treatment
- •Active infection requiring systemic treatment
- •History of interstitial lung disease
- •History of (noninfectious) pneumonitis that required steroids or current pneumonitis
- •Symptomatic ascites or pleural effusion
- •Previously had a stem cell or bone marrow transplant
- •Previously had a solid organ transplant
- •Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy
- •Known human immunodeficiency virus (HIV) and/or active and acute Hepatitis B or C infections
- •Not fully recovered from any effects of major surgery without significant detectable infection
- •Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
- •Had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study treatment, or has not recovered to Grade ≤1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
- •Expected to require any other form of antineoplastic therapy while participating in this study
- •On chronic systemic steroid therapy in excess of replacement doses (e.g., exceeding 10 mg/day of prednisone equivalent), or on any other form of immunosuppressive medication
- •Regular user (including "recreational use") of any illicit drugs at the time of signing informed consent, or has a recent history (within the last year) of substance abuse (including alcohol), as determined by the treating investigator. Participants who use cannabis for medicinal purposes or to treat specific symptoms will not be excluded unless it is being abused in the opinion of the treating investigator
- •Received a live-virus vaccine within 28 days before the first dose of study treatment
- •Currently participating and receiving study treatment in a study of an investigational agent or has participated and received study treatment in a study of an investigational agent or has used an investigational device within 28 days before the first dose of study treatment
- •Additional Exclusion Criteria for Participants in Arm 3:
- •Has received radiation therapy to the lung that is >30 Gray (Gy) within 6 months before the first dose of study treatment
- •Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
- •Is unable or unwilling to take folic acid or vitamin B12 supplementation
- •Additional Exclusion Criteria for Participants in Arm 4:
- •Has a known history of hypersensitivity or allergy to nab-paclitaxel or any of its components
- •Has neuropathy ≥Grade 2
- •Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of randomization
- •Has received previous treatment with immune checkpoint inhibitor(s) (eg, Programmed Cell Death Receptor 1 (PD-1)/PD-L1)
研究组 & 干预措施
Arm 1 Boserolimab 2 mg Q3W
Participants receive boserolimab 2 mg via intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 1 Boserolimab 7 mg Q3W
Participants receive boserolimab 7 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 1 Boserolimab 20 mg Q3W
Participants receive boserolimab 20 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 1 Boserolimab 70 mg Q3W
Participants receive boserolimab 70 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 1 Boserolimab 200 mg Q3W
Participants receive boserolimab 200 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 1 Boserolimab 700 mg Q3W
Participants receive boserolimab 700 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 1a Boserolimab 30 mg Q3W (Endometrial)
Participants with endometrial cancer receive boserolimab 30 mg via IV infusion once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 2 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 2 Boserolimab 2 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 2 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Pembrolizumab (Biological)
Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 7 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 2 Boserolimab 7 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 7 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Pembrolizumab (Biological)
Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 20 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 2 Boserolimab 20 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 20 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Pembrolizumab (Biological)
Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 70 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 2 Boserolimab 70 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 70 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Pembrolizumab (Biological)
Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 200 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 2 Boserolimab 200 mg Q3W + Pembrolizumab 200 mg Q3W
Participants receive separate IV infusions of boserolimab 200 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Pembrolizumab (Biological)
Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC)
Participants with triple-negative breast cancer (TNBC) receive separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 2a Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (TNBC)
Participants with triple-negative breast cancer (TNBC) receive separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Pembrolizumab (Biological)
Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial)
Participants with endometrial cancer receive separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 2b Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W (Endometrial)
Participants with endometrial cancer receive separate IV infusions of boserolimab 30 mg and pembrolizumab 200 mg. Boserolimab and pembrolizumab are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Each cycle is 3 weeks long.
干预措施: Pembrolizumab (Biological)
Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial)
Participants with endometrial cancer receive separate IV infusions of boserolimab 30 mg and pembrolizumab 400 mg. Boserolimab was administered once every 6 weeks (Q6W) on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 6 months). Pembrolizumab is administered once Q6W on Day 1 of each cycle for a total of up to approximately 18 cycles (up to approximately 27 months). Each cycle is 6 weeks long.
干预措施: Boserolimab (Drug)
Arm 2c Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W (Endometrial)
Participants with endometrial cancer receive separate IV infusions of boserolimab 30 mg and pembrolizumab 400 mg. Boserolimab was administered once every 6 weeks (Q6W) on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 6 months). Pembrolizumab is administered once Q6W on Day 1 of each cycle for a total of up to approximately 18 cycles (up to approximately 27 months). Each cycle is 6 weeks long.
干预措施: Pembrolizumab (Biological)
Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC)
Participants with non-small cell lung cancer (NSCLC) receive separate IV infusions of boserolimab 30 mg, pembrolizumab 200 mg, pemetrexed 500 mg/m^2, and carboplatin area under the curve (AUC) 5 mg/mL/min. Boserolimab is administered once Q3W on Day 1 of each cycle for a total of up to approximately 8 cycles (up to approximately 6 months). Pembrolizumab and pemetrexed are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Carboplatin is administered once Q3W on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 3 months). Each cycle is 3 weeks long.
干预措施: Boserolimab (Drug)
Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC)
Participants with non-small cell lung cancer (NSCLC) receive separate IV infusions of boserolimab 30 mg, pembrolizumab 200 mg, pemetrexed 500 mg/m^2, and carboplatin area under the curve (AUC) 5 mg/mL/min. Boserolimab is administered once Q3W on Day 1 of each cycle for a total of up to approximately 8 cycles (up to approximately 6 months). Pembrolizumab and pemetrexed are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Carboplatin is administered once Q3W on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 3 months). Each cycle is 3 weeks long.
干预措施: Pembrolizumab (Biological)
Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC)
Participants with non-small cell lung cancer (NSCLC) receive separate IV infusions of boserolimab 30 mg, pembrolizumab 200 mg, pemetrexed 500 mg/m^2, and carboplatin area under the curve (AUC) 5 mg/mL/min. Boserolimab is administered once Q3W on Day 1 of each cycle for a total of up to approximately 8 cycles (up to approximately 6 months). Pembrolizumab and pemetrexed are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Carboplatin is administered once Q3W on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 3 months). Each cycle is 3 weeks long.
干预措施: Pemetrexed (Drug)
Arm 3 Boserolimab 30 mg Q3W + Pembrolizumab 200 mg Q3W + Pemetrexed + Carboplatin (NSCLC)
Participants with non-small cell lung cancer (NSCLC) receive separate IV infusions of boserolimab 30 mg, pembrolizumab 200 mg, pemetrexed 500 mg/m^2, and carboplatin area under the curve (AUC) 5 mg/mL/min. Boserolimab is administered once Q3W on Day 1 of each cycle for a total of up to approximately 8 cycles (up to approximately 6 months). Pembrolizumab and pemetrexed are administered once Q3W on Day 1 of each cycle for a total of up to approximately 35 cycles (up to approximately 2 years). Carboplatin is administered once Q3W on Day 1 of each cycle for a total of up to approximately 4 cycles (up to approximately 3 months). Each cycle is 3 weeks long.
干预措施: Carboplatin (Drug)
Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC)
Participants with TNBC receive separate IV infusions of boserolimab 30 mg, pembrolizumab 400 mg, and nab-paclitaxel 100 mg/m^2. Boserolimab and pembrolizumab are administered once Q6W on Day 1 of each cycle for a total of up to approximately 18 cycles (up to approximately 27 months). Nab-paclitaxel is administered on a 3-weeks on/1-week off schedule every 28 days (Days 1, 8, 15, 29, and 36 of odd-numbered cycles and Days 1, 15, 22, and 29 of even-numbered cycles). Each cycle is 6 weeks long
干预措施: Boserolimab (Drug)
Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC)
Participants with TNBC receive separate IV infusions of boserolimab 30 mg, pembrolizumab 400 mg, and nab-paclitaxel 100 mg/m^2. Boserolimab and pembrolizumab are administered once Q6W on Day 1 of each cycle for a total of up to approximately 18 cycles (up to approximately 27 months). Nab-paclitaxel is administered on a 3-weeks on/1-week off schedule every 28 days (Days 1, 8, 15, 29, and 36 of odd-numbered cycles and Days 1, 15, 22, and 29 of even-numbered cycles). Each cycle is 6 weeks long
干预措施: Pembrolizumab (Biological)
Arm 4 Boserolimab 30 mg Q6W + Pembrolizumab 400 mg Q6W + Nab-paclitaxel (TNBC)
Participants with TNBC receive separate IV infusions of boserolimab 30 mg, pembrolizumab 400 mg, and nab-paclitaxel 100 mg/m^2. Boserolimab and pembrolizumab are administered once Q6W on Day 1 of each cycle for a total of up to approximately 18 cycles (up to approximately 27 months). Nab-paclitaxel is administered on a 3-weeks on/1-week off schedule every 28 days (Days 1, 8, 15, 29, and 36 of odd-numbered cycles and Days 1, 15, 22, and 29 of even-numbered cycles). Each cycle is 6 weeks long
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
时间窗: Up to 21 days in Cycle 1
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. A DLT was defined as any of the following events: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia requiring a platelet transfusion; Nonhematologic adverse event (AE) Grade ≥3, with exceptions; Grade 3 or 4 nonhematologic laboratory abnormality; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study drug discontinuation during the DLT evaluation period; Missing \>25% of any study drug during the DLT evaluation period due to a treatment-related AE; or Grade 5 toxicity. The number of participants who experienced one or more DLTs is reported.
Number of Participants With One or More AEs
时间窗: Up to approximately 78 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced one or more AEs is reported.
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to 23 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE is reported.
次要结局
- Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of Boserolimab(Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2)
- Arm 3 and 4: Number of Participants Who Discontinued Study Treatment Due to an AE(Up to 27 months)
- Area Under the Concentration-Time Curve From Time 0 to 3 Weeks (AUC0-3w) of Boserolimab(Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2)
- Area Under the Concentration-Time Curve From Time 0 to 6 Weeks (AUC0-6w) of Boserolimab(Arms 2c and 4 (Cycle = 6 weeks): Predose, at start & end of infusion on Day 1 Cycle 1, Days 2, 3, 8, 15, 22 of Cycle 1, and predose on Day 1 Cycle 2)
- Minimum Concentration (Cmin) of Boserolimab(Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2)
- Maximum Concentration (Cmax) of Boserolimab(Predose Day 1 Cycle 1 and at designated timepoints up to Day 1 Cycle 2)
- Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 78 months)
- Arm 3: Number of Participants Who Experienced a DLT(Up to 21 days in Cycle 1)
- Arm 4: Number of Participants Who Experienced a DLT(Up to 28 days in Cycle 1)
- Arm 3 and 4: Number of Participants With One or More AEs(Up to 57 months)