Esophageal Squamous Cell Carcinoma Clinical Trial
Official title:
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 (KEYMAKER-U06): Substudy 06B
This is a Phase 1/2, multicenter, randomized, open-label umbrella platform study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab and/or chemotherapy, for the treatment of participants with second line (2L) esophageal squamous cell carcinoma (ESCC) who have previously been exposed to PD-1/PD-L1 based treatment.
Status | Recruiting |
Enrollment | 200 |
Est. completion date | September 20, 2028 |
Est. primary completion date | November 7, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable ESCC. - Has 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-PD1/PD-L1 based therapy. - Has an evaluable baseline tumor sample (newly obtained or archival) for analysis. - Has adequately controlled blood pressure (BP) with or without antihypertensive medications. - Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to =Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have =Grade 2 neuropathy are eligible. Exclusion Criteria: - Direct invasion into adjacent organs such as the aorta or trachea. - Has experienced weight loss >10% over approximately 2 months prior to first dose of study therapy. - Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing. - Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease. - Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention. - Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication. - Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative therapy. - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Active autoimmune disease that has required systemic treatment in past 2 years. - History of human immunodeficiency virus (HIV) infection. - History of Hepatitis B or known active Hepatitis C virus infection. - History of allogenic tissue/solid organ transplant. - Clinically significant cardiovascular disease within 12 months from first dose of study intervention. - Known GI malabsorption or any other condition that may affect the absorption of lenvatinib. (Not applicable to actively enrolling arms as of Amendment 5) - Has risk for significant GI bleeding such as a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization, significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization. (Not applicable to actively enrolling arms as of Amendment 5) |
Country | Name | City | State |
---|---|---|---|
Brazil | Liga Norte Riograndense Contra o Câncer ( Site 4303) | Natal | Rio Grande Do Norte |
Brazil | Hospital Nossa Senhora da Conceição ( Site 4301) | Porto Alegre | Rio Grande Do Sul |
Brazil | ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 4300) | São Paulo | Sao Paulo |
Chile | Clínica las Condes ( Site 4403) | Santiago | Region M. De Santiago |
Chile | FALP-UIDO ( Site 4400) | Santiago | Region M. De Santiago |
China | Beijing Cancer hospital-Digestive Oncology ( Site 3500) | Beijing | Beijing |
China | Zhejiang Cancer Hospital-Thoracic oncology ( Site 3511) | Hangzhou | Zhejiang |
China | Anhui Provincil Hospital South District ( Site 3501) | Hefei | Anhui |
China | First Huai'an Hospital Affiliated to Nanjing Medical University ( Site 3506) | Huai'an | Jiangsu |
China | Shanghai Chest Hospital-Esophageal surgery department ( Site 3513) | Shanghai | Shanghai |
China | The First Affiliated Hospital of Xinxiang Medical University-Oncology ( Site 3510) | Xinxiang | Henan |
Germany | Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 4804) | Berlin | |
Germany | Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 4801) | Frankfurt | Hessen |
Italy | Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3200) | Milan | Lombardia |
Italy | Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative ( | Milano | |
Italy | Ospedale San Raffaele-Oncologia Medica ( Site 3202) | Milano | Lombardia |
Japan | National Cancer Center Hospital ( Site 3700) | Chuo-ku | Tokyo |
Japan | Saitama Prefectural Cancer Center ( Site 3703) | Ina-machi | Saitama |
Japan | National Cancer Center Hospital East ( Site 3701) | Kashiwa | Chiba |
Japan | Shizuoka Cancer Center ( Site 3704) | Nagaizumi-cho,Sunto-gun | Shizuoka |
Japan | Aichi Cancer Center Hospital ( Site 3702) | Nagoya | Aichi |
Korea, Republic of | Asan Medical Center-Department of Oncology ( Site 3901) | Seoul | |
Korea, Republic of | Samsung Medical Center-Division of Hematology/Oncology ( Site 3900) | Seoul | |
Norway | Oslo universitetssykehus, Radiumhospitalet ( Site 4501) | Oslo | |
Singapore | National University Hospital ( Site 3800) | Singapore | South West |
Switzerland | Kantonsspital Graubünden-Medizin ( Site 4700) | Chur | Grisons |
Switzerland | Hôpitaux Universitaires de Genève (HUG) ( Site 4702) | Genève | Geneve |
Taiwan | Chang Gung Memorial Hospital at Kaohsiung ( Site 4003) | Kaohsiung Niao Sung Dist | Kaohsiung |
Taiwan | China Medical University Hospital ( Site 4007) | Taichung | |
Taiwan | Taichung Veterans General Hospital-Radiation Oncology ( Site 4008) | Taichung | |
Taiwan | National Cheng Kung University Hospital ( Site 4001) | Tainan | |
Taiwan | National Taiwan University Hospital ( Site 4000) | Taipei | |
Taiwan | Taipei Veterans General Hospital ( Site 4005) | Taipei | |
Taiwan | Chang Gung Medical Foundation-Linkou Branch ( Site 4006) | Taoyuan | |
Thailand | Faculty of Medicine Siriraj Hospital ( Site 4102) | Bangkok | Krung Thep Maha Nakhon |
Turkey | Ankara Bilkent City Hospital-Medical Oncology ( Site 3405) | Ankara | |
Turkey | Hacettepe Universite Hastaneleri-oncology hospital ( Site 3402) | Ankara | |
Turkey | Atatürk Üniversitesi-onkoloji ( Site 3416) | Erzurum | |
Turkey | TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 3403) | Istanbul |
Lead Sponsor | Collaborator |
---|---|
Merck Sharp & Dohme LLC |
Brazil, Chile, China, Germany, Italy, Japan, Korea, Republic of, Norway, Singapore, Switzerland, Taiwan, Thailand, Turkey,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During Safety Lead-in Phase | A DLT is defined as any drug-related AE according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. | Up to approximately 3 weeks | |
Primary | Number of Participants Experiencing Adverse Events (AEs) During Safety Lead-in Phase | 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. | Up to approximately 3 weeks | |
Primary | Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented. | Up to approximately 3 weeks | |
Primary | Objective Response Rate (ORR) | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. | Up to approximately 92 weeks | |
Secondary | Progression-Free Survival (PFS) | PFS is defined as the time from allocation to the first documented progressive disease (PD) as assessed by RECIST 1.1 or death due to any cause, whichever occurs first. PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented. | Up to approximately 189 weeks | |
Secondary | Duration of Response (DOR) | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented. | Up to approximately 189 weeks | |
Secondary | Overall Survival (OS) | OS is defined as the time from the date of allocation to death from any cause. | Up to approximately 189 weeks | |
Secondary | Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase | 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. | Up to approximately 189 weeks | |
Secondary | Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase | 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. | Up to approximately 189 weeks |
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