Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma
Conditions
Keywords
stomach cancer, gastric cancer, esophageal cancer, digestive system diseases, gastrointestinal diseases, stomach diseases
Brief summary
The purpose of this study is to determine whether CRS-207 in combination with pembrolizumab is safe and effective in adults with recurrent or metastatic gastric, gastroesophageal junction, or esophageal cancer who have received one or two prior chemotherapy regimens for advanced disease.
Interventions
BIOLOGICALCRS-207
Administered by IV infusion over 1 hour.
BIOLOGICALPembrolizumab
Administered by IV infusion over 30 minutes.
Sponsors
Merck Sharp & Dohme LLC
Aduro Biotech, Inc.
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
1. Diagnosis with confirmed histology of one or more of the following: * Histologically-confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma (Siewert type II/III classification), or * Histologically-confirmed inoperable superior, medial, or distal third esophageal adenocarcinoma (Siewert type I classification may be included, provided there is no mixed histology) 2. Confirmed recurrent or metastatic disease 3. Received and experienced disease progression on, or following one or two prior chemotherapy regimens for advanced disease. 4. HER-2/neu negative or, if HER-2/neu positive, disease must have previously progressed on treatment with trastuzumab; prior treatment must have included a platinum and a fluoropyrimidine. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Can provide tissue for PD-L1 and mesothelin biomarker analysis 7. Adequate organ and marrow function at screening
Exclusion criteria
1. Diagnosis of squamous or undifferentiated gastric cancer 2. Individuals with inaccessible tumors or for whom biopsy is contraindicated 3. Participated in any other study in which receipt of an investigational new drug or investigational device occurred within 28 days of first dose of study drug 4. Receiving tumor necrosis factor (TNF) pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug 5. Clinical evidence of ascites by physical exam 6. Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug or has not recovered from adverse effects due to agents administered more than 4 weeks earlier 7. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of study drug, or has not recovered from adverse effects due to a previously-administered agent 8. Subjects who have implanted medical devices that pose high risks for colonization and cannot be easily removed (e.g. artificial heart valves, pacemakers, prosthetic joints, orthopedic screw(s), metal plate(s)) if infection occurs. Other common devices such as venous access devices (e.g. Port-a-Cath or Mediport) may be permitted as well as arterial and venous stents and dental and breast implants that were placed more than 3 months prior to first dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. | ORR was evaluated based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each evaluable subject as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and given the following hierarchy of overall response results: complete response (CR) \> partial response (PR) \> stable disease (SD) \> progressive disease (PD) \> not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR RECIST v1.1 values of CR, PR, SD, PD, and NE are provided for this outcome measure. . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. | The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per RECIST v1.1. |
| Progression-Free Survival (PFS) | Subjects followed for disease progression from first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. | Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) according to RECIST v1.1 or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). Subjects who do not experience PD and are alive on or before the data cut-off date will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier. |
| Duration of Response (DOR) | DOR assessed from the date of a post-baseline tumor assessment of CR or PR per RECIST v1.1 until the date of documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks. | Number of weeks from the first date a study subject achieved an objective disease response of CR or PR according to RECIST v1.1 to the date a study subject exhibited PD or death due to any cause, estimated using KM methods with 95% CIs. Subjects who do not experience PD or death at the time of analysis will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier. |
| Overall Survival (OS) | OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 15 weeks. | Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive, or the data cut-off date, whichever is earlier. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CRS-207 + Pembrolizumab Treatment cycle is once every 3 weeks. Pembrolizumab: 200 mg administered by IV infusion on Day 1 of each 3-week cycle. CRS-207: 1×10e9 CFU administered by IV infusion on Day 2 of Cycle 1, Day 1 of Cycles 2, 3, 4, and Day 1 every 6 weeks thereafter (every other cycle). | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Progression - subject went into hospice | 1 |
| Overall Study | Study Terminated by Sponsor | 2 |
Baseline characteristics
| Characteristic | CRS-207 + Pembrolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 58.6 years STANDARD_DEVIATION 13.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 1 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 4 / 5 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR was evaluated based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each evaluable subject as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and given the following hierarchy of overall response results: complete response (CR) \> partial response (PR) \> stable disease (SD) \> progressive disease (PD) \> not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR RECIST v1.1 values of CR, PR, SD, PD, and NE are provided for this outcome measure. .
Time frame: BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
Population: Analysis based upon subjects who received at least 1 dose of CRS-207 and had at least 1 evaluable post-baseline RECIST v1.1 tumor response assessment or were discontinued due to toxicity (the Evaluable Analysis Set \[EAS\]). 2 subjects did not have post-baseline tumor response assessments and could not be evaluated for this outcome measure.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CRS-207 + Pembrolizumab | Objective Response Rate (ORR) | Complete Response | 0 Participants |
| CRS-207 + Pembrolizumab | Objective Response Rate (ORR) | Partial Response | 0 Participants |
| CRS-207 + Pembrolizumab | Objective Response Rate (ORR) | Stable Disease | 0 Participants |
| CRS-207 + Pembrolizumab | Objective Response Rate (ORR) | Progressive Disease | 3 Participants |
| CRS-207 + Pembrolizumab | Objective Response Rate (ORR) | Not Evaluable | 0 Participants |
Secondary
Disease Control Rate (DCR)
The percentage of evaluable subjects who exhibited a post-baseline tumor assessment BOR rating of CR, PR, or SD per RECIST v1.1.
Time frame: BOR was assessed from the first post-baseline tumor assessment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CRS-207 + Pembrolizumab | Disease Control Rate (DCR) | 0 Participants |
Secondary
Duration of Response (DOR)
Number of weeks from the first date a study subject achieved an objective disease response of CR or PR according to RECIST v1.1 to the date a study subject exhibited PD or death due to any cause, estimated using KM methods with 95% CIs. Subjects who do not experience PD or death at the time of analysis will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier.
Time frame: DOR assessed from the date of a post-baseline tumor assessment of CR or PR per RECIST v1.1 until the date of documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
Population: No study subjects achieved CR or PR designation, therefore, per the final SAP DOR was not derived.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CRS-207 + Pembrolizumab | Duration of Response (DOR) | 0 Participants |
Secondary
Overall Survival (OS)
Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive, or the data cut-off date, whichever is earlier.
Time frame: OS was assessed from the first dose of study treatment until death or study termination, whichever is earlier, assessed up to 15 weeks.
Population: Analysis of OS was performed on subjects in the SAF.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CRS-207 + Pembrolizumab | Overall Survival (OS) | 11.57 weeks |
Secondary
Progression-Free Survival (PFS)
Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) according to RECIST v1.1 or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). Subjects who do not experience PD and are alive on or before the data cut-off date will be censored at the time of last evaluable tumor assessment or data cut-off date, whichever is earlier.
Time frame: Subjects followed for disease progression from first dose of study treatment until documented disease progression, initiation of new cancer treatment, death, or study termination, whichever is earlier, assessed up to 15 weeks.
Population: Analysis of PFS was performed on subjects in the SAF.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CRS-207 + Pembrolizumab | Progression-Free Survival (PFS) | 5.43 weeks |