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.
The master protocol is MK-3475-U06. As of Protocol Amendment 5, the Pembrolizumab Plus MK-4830 Plus Paclitaxel/Irinotecan arm and the Pembrolizumab Plus MK-4830 Plus Lenvatinib arm are no longer actively enrolling participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
230
80-100 mg/m\^2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.
180 mg/m\^2 IV infusion, administered on day 1 of every 14-day cycle.
200 mg IV infusion, administered every Q3W up to 35 infusions.
800 mg IV infusion, administered Q3W up to 35 infusions.
20 mg oral administration every day.
4 mg/kg or 5 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.
Administered per product label.
Administered per product label.
Administered per product label.
Administered per product label.
Administered per product label.
Participants are allowed to take supportive care measures for the management of adverse events associated with study intervention at the discretion of the investigator. Artificial tear drops or ointment may be given as a supportive care for Ocular Surface Toxicity.
University of Arizona Cancer Center-University of Arizona Cancer Center ( Site 4927)
Tucson, Arizona, United States
RECRUITINGUCLA Hematology/Oncology - Santa Monica ( Site 4905)
Los Angeles, California, United States
RECRUITINGHematology-Oncology Associates of Central NY, P.C. ( Site 4925)
East Syracuse, New York, United States
RECRUITINGColumbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 4907)
New York, New York, United States
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) 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.
Time frame: Up to approximately 3 weeks
Number of Participants Who Experienced an Adverse Event (AE) 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.
Time frame: Up to approximately 3 weeks
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.
Time frame: Up to approximately 3 weeks
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.
Time frame: Up to approximately 41 months
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.
Time frame: Up to approximately 70 months
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.
Time frame: Up to approximately 70 months
Overall Survival (OS)
OS is defined as the time from the date of allocation to death from any cause.
Time frame: Up to approximately 70 months
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.
Time frame: Up to approximately 70 months
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.
Time frame: Up to approximately 70 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
UPMC Hillman Cancer Center-UPMC ( Site 4904)
Pittsburgh, Pennsylvania, United States
RECRUITINGLiga Norte Riograndense Contra o Câncer ( Site 4303)
Natal, Rio Grande do Norte, Brazil
RECRUITINGHospital Nossa Senhora da Conceição ( Site 4301)
Porto Alegre, Rio Grande do Sul, Brazil
RECRUITINGICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 4300)
São Paulo, Brazil
RECRUITINGFALP-UIDO ( Site 4400)
Santiago, Region M. de Santiago, Chile
RECRUITINGCentro de Oncología de Precisión-Oncology ( Site 4404)
Santiago, Region M. de Santiago, Chile
RECRUITING...and 47 more locations