Esophageal Carcinoma, Esophagogastric Junction Carcinoma
Conditions
Keywords
Programmed Cell Death-1 (PD-1, PD1), Programmed Cell Death-Ligand 1 (PD-L1, PDL1), Programmed Cell Death-Ligand 2 (PD-L2, PDL2)
Brief summary
In this study participants with advanced/metastatic adenocarcinoma of the esophagus (EAC), squamous cell carcinoma of the esophagus (ESCC), or advanced/metastatic Siewert type I adenocarcinoma of the esophagogastric junction (EGJ), who had been previously treated with two standard therapies, will be treated with pembrolizumab.
Interventions
BIOLOGICALpembrolizumab
IV Q3W
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy greater than 3 months * Histologically-proven advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ * Documented objective radiographic or clinical disease progression on two previous lines of standard therapy * Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 * Can provide either a newly obtained or archival tumor tissue sample for intratumoral immune-related testing and for anti-programmed cell death (PD-1) * Female participants of childbearing potential must be willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication * Male participants must agree to use adequate contraception starting with the first dose through 120 days after the last dose of study medication * Adequate organ function
Exclusion criteria
* Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study medication * Has active autoimmune disease that has required systemic treatment within the 2 years prior to the first dose of study medication * Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication * Known central nervous system (CNS) metastases and/or carcinomatous meningitis * Prior anti-cancer mAb, chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study medication or not recovered from adverse events due to a previously administered agent * Prior therapy with an anti-PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or previously participated in a Merck pembrolizumab (MK-3475) study * Has a known additional malignancy that has progressed or required active treatment within the last 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, in-situ cervical cancer, and in-situ or intra-mucosal pharyngeal cancer * Received a live vaccine within 30 days of the first dose of study medication * Known history of Human Immunodeficiency Virus (HIV) infection * Known active Hepatitis B or C * History of non-infectious pneumonitis that required steroids or current pneumonitis * Active infection requiring systemic therapy * Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study * Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) According to Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) | Up to approximately 28 months | ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR based on modified RECIST 1.1 was reported per protocol for the first course of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 59 months | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants who experienced ≥1 AE was reported per protocol for the first course of treatment. |
| Number of Participants That Discontinued Study Treatment Due to an AE | Up to approximately 24 months | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants that discontinued study treatment due to an AE was reported per protocol for the first course of treatment. |
| Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR | Up to approximately 67 months | For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported per protocol for the first course of treatment. |
| Progression Free Survival (PFS) According to RECIST 1.1 Assessed by BICR | Up to approximately 67 months | PFS was defined as the time from first day of study treatment to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 was reported per protocol for the first course of treatment. |
| Overall Survival (OS) | Up to approximately 67 months | OS was defined as the time from first day of study treatment to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was reported per protocol for the first course of treatment |
Participant flow
Pre-assignment details
Of 185 participants screened for inclusion, 121 were enrolled and received treatment. Per protocol, response/progression or adverse events (AEs) that occurred during the second course were not counted towards efficacy outcome measures or safety outcome measures, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab 200 mg Participants received pembrolizumab 200 mg, intravenously (IV), every 3 weeks (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 121 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 112 |
| Overall Study | Sponsor Decision | 5 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Pembrolizumab 200 mg |
|---|---|
| Age, Continuous | 63.5 Years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 108 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 42 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 71 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 116 / 121 | 0 / 1 |
| other Total, other adverse events | 107 / 121 | 1 / 1 |
| serious Total, serious adverse events | 47 / 121 | 0 / 1 |
Outcome results
Primary
Objective Response Rate (ORR) According to Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR)
ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR based on modified RECIST 1.1 was reported per protocol for the first course of treatment.
Time frame: Up to approximately 28 months
Population: All allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab 200 mg | Objective Response Rate (ORR) According to Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) | 9.9 percentage of participants |
Secondary
Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR
For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported per protocol for the first course of treatment.
Time frame: Up to approximately 67 months
Population: All allocated participants who received at least 1 dose of study treatment and who experienced a confirmed CR or confirmed PR. One previously reported participant was excluded from the DOR analysis based on a BICR re-read of prior scans after the primary analysis database lock.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Duration of Response (DOR) According to RECIST 1.1 Assessed by BICR | 19.7 Months |
Secondary
Number of Participants That Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants that discontinued study treatment due to an AE was reported per protocol for the first course of treatment.
Time frame: Up to approximately 24 months
Population: All allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab 200 mg | Number of Participants That Discontinued Study Treatment Due to an AE | 14 Participants |
Secondary
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants who experienced ≥1 AE was reported per protocol for the first course of treatment.
Time frame: Up to approximately 59 months
Population: All allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab 200 mg | Number of Participants Who Experienced an Adverse Event (AE) | 116 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from first day of study treatment to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was reported per protocol for the first course of treatment
Time frame: Up to approximately 67 months
Population: All allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Overall Survival (OS) | 5.8 Months |
Secondary
Progression Free Survival (PFS) According to RECIST 1.1 Assessed by BICR
PFS was defined as the time from first day of study treatment to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 was reported per protocol for the first course of treatment.
Time frame: Up to approximately 67 months
Population: All allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg | Progression Free Survival (PFS) According to RECIST 1.1 Assessed by BICR | 2.0 Months |