EUCTR2021-005443-76-DE进行中（未招募）1 期
A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer Previously Exposed to PD-1/PD-L1 Treatment (KEYMARKER-U06): Substudy 06B. - Substudy 06B: Phase 1/2 Umbrella Study of Combination Therapies in Esophageal Cancer
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 82
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1.Histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic ESCC
- •2.Have a life expectancy of > 3 months
- •3.Measurable disease per RECIST 1.1 as determined by the local site investigator/radiology assessment and verified by BICR. A lesion(s) situated in a previously irradiated area can be considered a target lesion(s) if progression has been demonstrated and the lesion(s) is considered measurable per RECIST 1.1 criteria
- •4.Experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy that includes a platinum agent and previous exposure to an anti–PD-1/PD-L1 based IO therapy (either as a combination or monotherapy). This study will only include 2L participants who have progressed during or after receiving at least one dose of platinum-based chemotherapy and must have received at least 2 doses of PD-1/PD-L1 inhibitors given in a 1L setting and had documented disease progression
- •5.Submits an evaluable baseline tumor sample (newly obtained or archival) for analysis. Newly obtained biopsies are preferred to archived tissue
- •6.Performance status of 0 or 1 on the ECOG Performance Scale before first dose of study intervention.
- •7.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 allocation/randomization
- •8.Participants with a feeding tube to maintain adequate nourishment and for the administration of medications are allowed
- •9.Adequate organ function. Specimens must be collected within 7 days before the start of study intervention
- •10.Participants are at least 18 years of age on the day of providing documented informed consent
- •11.If male, agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose. The length of time required to continue contraception for each study intervention:
- •-Chemotherapy: 90 days
- •-Lenvatinib: 7 days
- •-Pembrolizumab and MK-4830: no contraception requirements
- •-MK-2870: 100 days
- •Refrains from donating sperm
- •PLUS either:
- •Abstains from heterosexual intercourse as their preferred and usual lifestyle and agrees to remain abstinent
- •Uses contraception unless confirmed to be azoospermic as detailed below:
- •- Uses 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. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed
- •12.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- •Not a WOCBP
- •A WOCBP and:
- •- Uses a contraceptive method highly effective (failure rate <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 the time needed to eliminate each study intervention after the last dose and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during
排除标准
- •1.Direct invasion into adjacent organs such as the aorta or trachea (T4b disease)
- •2.Experienced weight loss >10% over approximately 2 months prior to first dose of study therapy
- •3.Clinically apparent ascites or pleural effusion by physical examination
- •4.Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
- •5. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
- •6.Received prior therapy with:
- •-Anti-VEGF TKI (including lenvatinib) or anti-VEGF mAb
- •-Any agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
- •-An agent targeting ILT4 or HLA-G
- •-A TROP2-targeted ADC
- •-A topoisomerase I inhibitor-containing ADC
- •7.Requires treatment with a strong inhibitor or inducer of CYP3A4 at least 14 days before the first dose of study intervention and throughout the study.
- •8.Received prior systemic anticancer therapy within 2 weeks before allocation/randomization
- •9.Received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids.
- •10.Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
- •11. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
- •12.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
- •13.Known additional malignancy that is progressing or has required active treatment within the past 3 years
- •14.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 as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention
- •15.Severe hypersensitivity (Grade =3) to any study intervention and/or any of its excipients or other biologic therapy
- •16.Active autoimmune disease that has required systemic treatment in 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
- •17.History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •18.Active infection requiring systemic therapy
- •19.History of HIV infection. HIV testing is not required unless mandated by local health authority
- •20.History of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as detectable HCV RNA [qualitative]) infection
- •21.History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the individual's ability to cooperate with the requirements of the study, or interfere with the individual's participation for the full d
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