EUCTR2019-003609-84-FR进行中（未招募）1 期
A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants with RCC (U03): Substudy 03A - Substudy 03A: Phase 1b/2 Umbrella Study of Combination Therapies in RCC
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc0 个研究点目标入组 430 人开始时间: 2020年10月28日最近更新:
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 430
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC (with or without sarcomatoid features), ie, Stage IV RCC per AJCC
- •2. Has received no prior systemic therapy for advanced RCC. [1L participants]
- •3. Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- •4. Has a KPS =70% assessed =10 days prior to randomization/allocation.
- •5. Is able to swallow oral medication
- •6. Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
- •7. Has adequate organ function. Specimens must be collected within 10 days prior to the start of study intervention
- •8. Participants receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks prior to randomization/allocation
- •9. If participants received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention
- •10. Has adequately controlled BP with or without antihypertensive medications, defined as BP =150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization/allocation
- •11. Is male or female, from 18 years to 120 years of age inclusive, at the time of signing the informed consent
- •12. Male participants are eligible to participate if they agree to the following during treatment with and for at least 5 days after the last dose of lenvatinib and/or MK-6482:
- •- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
- •- Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
- •Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant
- •- Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- •13. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- •- Is not a WOCBP
- •- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of pembrolizumab, MK 1308A and MK-4280A or 30 days after the last dose of lenvatinib and MK-6482, whichever occurs last
- •- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention
- •- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
- •- The investigator is responsible for review of medical history, menstrual history, and recent sexual activi
排除标准
- •1. Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 12 months from Day 1 of study intervention administration, or New York Heart Association Class III or IV congestive heart failure, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Medically controlled arrhythmia stable on medication is permitted
- •2. Prolongation of QTcF interval to >480 ms
- •3. Has a LVEF below the institutional (or local laboratory) normal range as determined by MUGA or ECHO
- •4. Has had major surgery within 3 weeks prior to first dose of study interventions
- •5. Has urine protein =1 g/24 hours
- •6. Has a history of interstitial lung disease, history of (non-infectious) pneumonitis that required steroids, or has current pneumonitis
- •7. Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain). A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible
- •8. Has a history of inflammatory bowel disease
- •9. Has preexisting =Grade 3 GI or non-GI fistula
- •10. Has malabsorption due to prior GI surgery or GI disease
- •11. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease
- •12. Has received a live or live attenuated vaccine within 30 days before the first dose of study drug.
- •13. Is currently participating in a study of an investigational agent or is currently using an investigational device
- •14. Participants who have been previously allocated/randomized to study intervention in any substudy of protocol MK-3475-U03
- •15. 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 the first dose of study drug
- •16. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- •17. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
- •18. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
- •19. Has a history of hypersensitivity reaction to any of the investigational agent(s) included in this study. For example, but not limited to:
- •- Has a severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients
- •- Has a history of severe hypersensitivity reaction (eg, generalized rash/erythema, hypotension, bronchospasm, angioedema, or anaphylaxis) to lenvatinib
- •20. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
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