Esophageal Squamous Cell Carcinoma (ESCC)
Conditions
Keywords
Esophageal cancer, Programmed Cell Death 1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL-1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL-2, PD-L2)
Brief summary
This is a phase I/II multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of investigational agents with pembrolizumab, plus chemotherapy or lenvatinib, for the treatment of participants with advanced esophageal cancer who have failed 1 prior line of therapy and have not been previously exposed to programmed cell death 1 protein (PD-1)/ programmed cell death ligand 1 (PD-L1) based treatment. With protocol amendment 5 (effective: 17-November-2023), enrollment in study arms Pembrolizumab plus MK-4830 plus Chemotherapy and Pembrolizumab plus MK-4830 plus lenvatinib is discontinued.
Detailed description
The master protocol is MK-3475-U06.
Interventions
BIOLOGICALPembrolizumab
200 mg administered via intravenous (IV) infusion every 3 weeks (Q3W)
BIOLOGICALCoformulation favezelimab/pembrolizumab
800 mg favezelimab + 200 mg pembrolizumab administered via IV infusion on day 1 and then Q3W
BIOLOGICALMK-4830
800 mg administered via IV infusion Q3W
DRUGLenvatinib
20 mg administered via oral capsules each day
DRUGIrinotecan
180 mg/m\^2 administered via IV infusion on day 1 of every 14-day cycle.
DRUGPaclitaxel
80-100 mg/m\^2 administered via IV infusion on Days 1, 8 and 15 of every 28 day cycle
Sponsors
Merck Sharp & Dohme LLC
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 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. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase | Up to approximately 3 weeks | A DLT is defined as any drug-related adverse event (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. |
| Number of Participants Experiencing an Adverse Event (AE) During Safety Lead-in Phase | Up to approximately 3 Weeks | 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. |
| Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase | Up to approximately 3 weeks | 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. |
| Objective Response Rate (ORR) | Up to approximately 40 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 40 months | 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. |
| Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase | Up to approximately 104 weeks | 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. |
| Duration of Response (DOR) | Up to approximately 40 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 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. |
| Overall Survival (OS) | Up to approximately 40 months | OS is defined as the time from the date of allocation to death from any cause. |
| Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase | Up to approximately 40 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. 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. |
Countries
Brazil, Chile, France, Germany, Italy, Japan, Norway, Singapore, South Korea, Switzerland, Taiwan, Thailand, Turkey (Türkiye)
Outcome results
None listed