Esophageal Squamous Cell Carcinoma
Conditions
Brief summary
Researchers are looking for new ways to treat esophageal squamous cell carcinoma (ESCC). ESCC is a type of cancer that starts in certain cells that line the esophagus. The esophagus is the tube that connects the throat to the stomach. This study will look at ESCC that is either locally advanced unresectable, which means it has spread into tissue near where it started and cannot be completely removed by surgery, or metastatic, which means it has spread to other body parts. Available treatments for these types of ESCC include pembrolizumab and chemotherapy. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing. Researchers want to learn about giving pembrolizumab and investigational agents, with or without chemotherapy to treat ESCC. Ifinatamab deruxtecan (I-DXd), is an antibody-drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The main goal of this study is to learn about the safety of investigational agents and pembrolizumab with or without chemotherapy and if people tolerate them. Researchers also want to learn how cancer responds (gets smaller or goes away) to the study treatments.
Detailed description
The master protocol is MK-3475-U06.
Interventions
BIOLOGICALPembrolizumab
IV infusion
BIOLOGICALI-DXd
IV infusion
DRUGLeucovorin
IV infusion
DRUGLevoleucovorin
IV infusion
DRUG5-Fluorouracil (5-FU)
IV Infusion
DRUGOxaliplatin
IV infusion
BIOLOGICALSacituzumab tirumotecan
IV infusion
DRUGRescue Medication
Includes 5-HT3 receptor antagonist, NK-1 receptor antagonist, and corticosteroid for Arms 2, 3, and 4, and H1 receptor antagonist, H2 receptor antagonist, acetaminophen, and dexamethasone for Arm 5, administered per approved product label
Sponsors
Merck Sharp & Dohme LLC
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic squamous cell carcinoma of the esophagus in first-line (1L) setting. * Has measurable disease per RECIST 1.1 as assessed by the local site. investigator or designee/radiology assessment and verified by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions. * Has AEs due to previous anticancer therapies of ≤Grade 1 or baseline (except alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone replacement are acceptable. * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART). * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Has adequate organ function.
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase | Up to approximately 28 days | Percentage of participants experiencing toxicities that are possibly, probably, or definitely related to study intervention; that meet pre-defined severity criteria; and result in a change in the given dose. |
| Percentage of Participants who Experience an Adverse Event (AE) | Up to approximately 77 months | 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. The percentage of participants who experience an AE will be reported. |
| Objective Response Rate (ORR) | Up to approximately 77 months | ORR is defined as a confirmed complete response (CR: the 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 (RECIST) 1.1 as assessed by blinded independent central review (BICR). The percentage of participants who experience CR or PR as assessed by BICR will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to approximately 77 months | 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 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. |
| Progression-Free Survival (PFS) | Up to approximately 77 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. 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. PFS as assessed by BICR will be presented. |
| Overall Survival (OS) | Up to approximately 77 months | OS is defined as the time from allocation/randomization to death due to any cause. |
| Disease Control Rate (DCR) | Up to approximately 77 months | DCR is defined as a confirmed complete response (CR) or partial response (PR), or stable disease (SD) with at least 6 months PFS per RECIST 1.1 as assessed by BICR. |
| Maximum Plasma Concentration (Cmax) of I-DXd | At designated time points up to approximately 65 months | Cmax is defined as the peak level I-DXd reaches in the blood plasma. Blood samples collected predose and at multiple timepoints postdose will be used to determine the Cmax of I-DXd when co-administered with other investigational agents. |
| Time to Maximum Plasma Concentration (Tmax) of I-DXd | At designated time points up to approximately 65 months | Tmax is defined as the time it took I-DXd to reach its peak level in blood plasma. Blood samples collected predose and at designated timepoints postdose will be used to determine the Tmax of I-DXd when co-administered with other investigational agents. |
| Area Under the Concentration-Time Curve from Time 0 to Last Measurable Plasma Concentration (AUClast) of I-DXd | At designated time points up to approximately 65 months | AUClast is defined as the area under the concentration-time curve from time 0 to the last measurable concentration of I-DXd in the blood plasma. Blood samples collected at predose and at designated timepoints postdose will be used to determine the AUClast of I-DXd in combination with other agents. |
| Area Under the Concentration-Time Curve from Time 0 to the End of the Dosing Period (AUCtau) of I-DXd | At designated time points up to approximately 65 months | AUCtau is defined as the area under the concentration-time curve from time zero to the end of the dosing period. Blood samples collected at predose and at designated timepoints postdose will be used to determine the AUCtau of I-DXd in combination with other agents. |
| The Percentage of Participants with Antidrug Antibodies (ADA) Against I-DXd | Up to approximately 65 months | Blood samples collected at designated timepoints will be used to determine the ADA response to I-DXd. The percentage of participants with ADA will be reported. |
| The Percentage of Participants with Treatment-Emergent ADA Against I-DXd | Up to approximately 65 months | Blood samples collected at designated timepoints will be used to determine the treatment-emergent ADA response to I-DXd. The percentage of participants who have treatment-emergent I-DXd ADA will be reported. |
Countries
Brazil, Chile, China, Czechia, France, Germany, Italy, Japan, Norway, Singapore, South Korea, Switzerland, Taiwan, Thailand, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed