Clinical trial NCT02981524: Study of GVAX (With CY) and Pembrolizumab in MMR-p Advanced Colorectal Cancer
Official title: A Phase 2 Study of GVAX Colon Vaccine (With Cyclophosphamide) and Pembrolizumab in Patients With Mismatch Repair-Proficient (MMR-p) Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Colorectal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-12-05
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to 1 year
Secondary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: up to 1 year
measure: Progression Free Survival (PFS)
timeFrame: up to 1 year
measure: Overall Survival (OS)
timeFrame: Up to 1 year
measure: Duration of Response (DOR)
timeFrame: 1 year
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Nilofer Azad, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yarchoan M, Huang CY, Zhu Q, Ferguson AK, Durham JN, Anders RA, Thompson ED, Rozich NS, Thomas DL 2nd, Nauroth JM, Rodriguez C, Osipov A, De Jesus-Acosta A, Le DT, Murphy AG, Laheru D, Donehower RC, Jaffee EM, Zheng L, Azad NS. A phase 2 study of GVAX colon vaccine with cyclophosphamide and pembrolizumab in patients with mismatch repair proficient advanced colorectal cancer. Cancer Med. 2020 Feb;9(4):1485-1494. doi: 10.1002/cam4.2763. Epub 2019 Dec 26.