Metastatic Colorectal Cancer
Conditions
Keywords
Colorectal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Intestinal Diseases, Rectal Diseases, Colonic Diseases
Brief summary
This study will be looking at the objective response rate (ORR) as measured by RECIST in in patients with mismatch repair-proficient (MMR-p), advanced colorectal cancer that treated with CY/GVAX in combination with Pembrolizumab.
Interventions
Sponsors
Merck Sharp & Dohme LLC
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Documented mismatch repair-proficient cancer of colorectum, who have received at least two prior lines of therapy for metastatic disease 2. Measurable disease by RECIST v1.1 3. Age \>18 years 4. ECOG Performance Status of 0 to 1 5. Estimated life expectancy of greater than 3 months. 6. Adequate organ function as defined by study-specified laboratory tests 7. Must use acceptable form of birth control through the study and for 120 days after final dose of study drug 8. Signed informed consent form 9. Willing and able to comply with study procedures
Exclusion criteria
1. Has a known additional malignancy that is progressing or requires active treatment. 2. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. 3. Has known malignant small bowel obstruction within the last 6 months. 4. Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions. 5. Systemically active steroid use. 6. Has an active infection requiring systemic therapy. 7. Has a known history of active TB (Bacillus Tuberculosis). 8. Infection with HIV or hepatitis B or C. 9. Has history of (non-infectious) pneumonitis that required steroids. 10. Must not require supplemental oxygen or have a pulse oximetry \< 92% on room air. 11. Conditions, including therapy, laboratory abnormalities, psychiatric or substance abuse disorders, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures. 12. Pregnant or lactating. 13. Another investigational product within 28 days prior to receiving study drug. 14. Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug. 15. Chemotherapy, radiation, hormonal, or biological cancer therapy within 28 days prior to receiving study drug. 16. Has received a live vaccine within 30 days of planned start of study therapy. 17. Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.). 18. Patients receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug administration. 19. Hypersensitivity to pembrolizumab or any of its excipients. 20. Patient has a known or suspected hypersensitivity to GM-CSF, hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of GVAX vaccine. 21. Presence of any tissue or organ allograft and history of allogeneic hematopoietic stem cell transplant. 22. Unwilling or unable to comply with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | up to 1 year | ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | up to 1 year | Number of participants who experience treatment related adverse events ≥ grade 3 as defined by CTCAE 4.0. |
| Progression Free Survival (PFS) | up to 1 year | Progression-free Survival (PFS) is defined as the number of days from cycle 1, day 1 of immunotherapy until first documented local progression or death due to any cause. PD is \>20% increase in sum of diameters of target lesions as assessed using RECIST (version 1.1). |
| Overall Survival (OS) | Up to 1 year | OS is defined as the number of days from start of study treatment to time of death. Individuals will be censored at the date of the last study visit if no event occurs. The estimation method used was Kaplan-Meier. |
| Duration of Response (DOR) | 1 year | Number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1, CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CY/GVAX With Pembrolizumab During each 21 day cycles, Cyclophosphamide (CY) is administered on Day 1 at 200 mg/m2 followed by Pembrolizumab at 200mg, the colon cancer vaccine (GVAX) is administered on Day 2 at 5E8 colon cancer cells + 5E7 GM-CSF secreting cells.
CY: CY is administered intravenously at 200 mg/m2
GVAX: GVAX is administered intradermally at 5E8 colon cancer cells + 5E7 GM-CSF secreting
Pembrolizumab: Pembrolizumab is administered intravenously at 200 mg | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death (unrelated) | 1 |
| Overall Study | Progressive Disease | 14 |
| Overall Study | Treatment Related Toxicity | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | CY/GVAX With Pembrolizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Baseline Carcinoembryonic Antigen (CEA) | 84.8 ng/ml |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 0 | 6 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 1 | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 17 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 14 / 17 |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 6 / 17 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.
Time frame: up to 1 year
Population: Data to assess objective response was only collected from 14/17 participants. The remaining 3 patients were withdrawn from study therapy for early clinical progression and were not evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CY/GVAX With Pembrolizumab | Objective Response Rate (ORR) | 0 Participants |
Secondary
Duration of Response (DOR)
Number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1, CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions.
Time frame: 1 year
Population: There were no patients that had a CR or PR. Therefore, data could not be collected to assess this outcome measure.
Secondary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Number of participants who experience treatment related adverse events ≥ grade 3 as defined by CTCAE 4.0.
Time frame: up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CY/GVAX With Pembrolizumab | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 6 Participants |
Secondary
Overall Survival (OS)
OS is defined as the number of days from start of study treatment to time of death. Individuals will be censored at the date of the last study visit if no event occurs. The estimation method used was Kaplan-Meier.
Time frame: Up to 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CY/GVAX With Pembrolizumab | Overall Survival (OS) | 213 days |
Secondary
Progression Free Survival (PFS)
Progression-free Survival (PFS) is defined as the number of days from cycle 1, day 1 of immunotherapy until first documented local progression or death due to any cause. PD is \>20% increase in sum of diameters of target lesions as assessed using RECIST (version 1.1).
Time frame: up to 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CY/GVAX With Pembrolizumab | Progression Free Survival (PFS) | 82 days |