Study of GVAX (With CY) and Pembrolizumab in MMR-p Advanced Colorectal Cancer

NCT02981524 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: J16154IRB00114053MISP53919
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  up to 1 year

Secondary Outcomes (4)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  up to 1 year

• Progression Free Survival (PFS)

  up to 1 year

• Overall Survival (OS)

  Up to 1 year

• Duration of Response (DOR)

  1 year

Study Arms (1)

CY/GVAX with Pembrolizumab

EXPERIMENTAL

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 for the first 4 cycles of treatment. After cycle 4, cyclophosphamide and GVAX will be administered with every 4th cycle.

Drug: CY; Biological: GVAX; Drug: Pembrolizumab

Interventions

CY DRUG

CY is administered intravenously at 200 mg/m2

Also known as: Cyclophosphamide, Cytoxan

CY/GVAX with Pembrolizumab

GVAX BIOLOGICAL

GVAX is administered intradermally at 5E8 colon cancer cells + 5E7 GM-CSF secreting

Also known as: Colon cancer vaccine

CY/GVAX with Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is administered intravenously at 200 mg

Also known as: KEYTRUDA, MK-3475

CY/GVAX with Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented mismatch repair-proficient cancer of colorectum, who have received at least two prior lines of therapy for metastatic disease
• Measurable disease by RECIST v1.1
• Age \>18 years
• ECOG Performance Status of 0 to 1
• Estimated life expectancy of greater than 3 months.
• Adequate organ function as defined by study-specified laboratory tests
• Must use acceptable form of birth control through the study and for 120 days after final dose of study drug
• Signed informed consent form
• Willing and able to comply with study procedures

You may not qualify if:

• Has a known additional malignancy that is progressing or requires active treatment.
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has known malignant small bowel obstruction within the last 6 months.
• Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions.
• Systemically active steroid use.
• Has an active infection requiring systemic therapy.
• Has a known history of active TB (Bacillus Tuberculosis).
• Infection with HIV or hepatitis B or C.
• Has history of (non-infectious) pneumonitis that required steroids.
• Must not require supplemental oxygen or have a pulse oximetry \< 92% on room air.
• 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.
• Pregnant or lactating.
• Another investigational product within 28 days prior to receiving study drug.
• Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug.
• Chemotherapy, radiation, hormonal, or biological cancer therapy within 28 days prior to receiving study drug.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Related Publications (1)

• 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.

  PMID: 31876399 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Colonic Diseases

Interventions

Cyclophosphamide; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Nilofer Azad, MD
• Organization: Sidney Kimmel Cancer Center at Johns Hopkins

nazad2@jhmi.edu

410-614-9169

Study Officials

• Nilofer Azad, MD

  The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 5, 2016
• Study Start: May 26, 2017
• Primary Completion: March 20, 2018
• Study Completion: March 20, 2018
• Last Updated: February 10, 2021
• Results First Posted: October 8, 2019

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)