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Phase 1 Study of MGD007 in Relapsed/Refractory Metastatic Colorectal Carcinoma

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by MacroGenics
Sponsor:
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT02248805
First received: September 18, 2014
Last updated: February 8, 2017
Last verified: February 2017
  Purpose
The primary goal of this Phase 1 study is to characterize the safety and tolerability of MGD007 and establish the maximum tolerated dose (MTD) of MGD007 administered on either weekly or every three week schedules of administration among patients with metastatic colorectal carcinoma. Pharmacokinetics, pharmacodynamics, and the anti-tumor activity of MGD007 will also be assessed.

Condition Intervention Phase
Colorectal Carcinoma Drug: MGD007 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-Human, Open Label, Dose Escalation Study of MGD007, A Humanized gpA33 x CD3 Dual-Affinity Re-Targeting (DART®) Protein in Patients With Relapsed/Refractory Metastatic Colorectal Carcinoma

Further study details as provided by MacroGenics:

Primary Outcome Measures:
  • Characterize dose limiting toxicity and establish a maximum tolerated dose and schedule [ Time Frame: Cycle 1 of a 6 week cycle ]
    Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit. The MTD will be defined separately for both the weekly and every three week schedules of MGD007 administration, and will be determined as the highest dose level at which the incidence of DLT is < 33% during the first cycle of MGD007 treatment.


Secondary Outcome Measures:
  • Characterize the PK and Immunogenicity of MGD07 [ Time Frame: Beginning of treatment through end of treatment, an expected duration of less than 12 months ]
    Serum concentrations of MGD007 will be monitored. PK modeling will be performed and an appropriate model will be selected to describe the data.

  • Describe any evidence of anti-tumor activity [ Time Frame: Every 6 weeks until End of Study, an expected duration of less than 12 months ]
    Obtain regular radiographic and clinical evaluations to assess treatment response.


Estimated Enrollment: 158
Study Start Date: September 2014
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Does Escalation Arm A
MGD007 treatment once weekly
Drug: MGD007
MGD007 is a gpA33 x CD3 bi-specific antibody-based molecular construct referred to as a dual affinity re-targeting (DART) molecule. MGD007 will be administered as a single agent.
Experimental: Dose Escalation Arm B
MGD007 treatment once every 3 weeks
Drug: MGD007
MGD007 is a gpA33 x CD3 bi-specific antibody-based molecular construct referred to as a dual affinity re-targeting (DART) molecule. MGD007 will be administered as a single agent.
Experimental: Dose Expansion Arm C
MGD007 for K-ras wild-type metastatic CRC
Drug: MGD007
MGD007 is a gpA33 x CD3 bi-specific antibody-based molecular construct referred to as a dual affinity re-targeting (DART) molecule. MGD007 will be administered as a single agent.
Experimental: Dose Expansion Arm D
MGD007 for K-ras mutant metastatic CRC
Drug: MGD007
MGD007 is a gpA33 x CD3 bi-specific antibody-based molecular construct referred to as a dual affinity re-targeting (DART) molecule. MGD007 will be administered as a single agent.

Detailed Description:

This is a two-arm open-label, multi-center, Phase 1 dose-escalation study to define a MTD, describe preliminarily safety, and to assess PK, immunogenicity, and potential anti-tumor activity of MGD007 administered on either weekly or every three week schedules in patients with relapsed or refractory metastatic colorectal cancer.

In the initial phase of the study, two dose schedules will be assessed in dose escalation, once weekly and once every three weeks administration of single agent MGD007. Following the establishment of an MTD, additional patients will enroll in two separate dose expansion cohorts at that treatment dose and schedule.

In all segments of the study, patients who benefit from MGD007 treatment and continue to meet eligibility may continue treatment in Cycles 2 and beyond.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For the dose escalation cohorts, histologically-proven metastatic colorectal adenocarcinoma that is refractory to 2 prior standard treatment regimens or standard treatment was declined.
  • For the dose expansion cohorts, histologically-proven metastatic colorectal adenocarcinoma that is refractory to 1 prior standard treatment regimen or standard therapy was declined.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of at least 12 weeks
  • Measurable disease
  • Intolerance to at least 2 prior standard therapy regimens
  • Acceptable laboratory parameters
  • Adult (≥18 years old)

Exclusion Criteria:

  • Known brain metastasis
  • Any prior history of or suspected current autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease)
  • Prior history of allogeneic bone marrow, stem-cell, or solid organ transplantation
  • Prior treatment with checkpoint inhibitors and other immunotherapy treatments, including anti-LAG-3, anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibodies, if less than 5 half lives before study drug administration
  • Prior history of Grade 3 or greater drug-related diarrhea/colitis during treatment with checkpoint inhibitors or other immunotherapy treatments.
  • Treatment with any local or systemic anti-neoplastic therapy or any other investigational agent in the 4 weeks prior to study drug administration
  • Require, at the time of study entry, treatment with steroids > 10 mg/day of oral prednisone (or equivalent), except topical use, steroid inhaler, nasal spray or ophthalmic solution
  • History of clinically significant cardiovascular disease, gastrointestinal disorder, or significant pulmonary compromise.
  • Second primary malignancy that has not been in remission for greater than 3 years, with the exception of non-melanoma skin cancer, cervical carcinoma in situ,or squamous intraepithelial lesion on PAP smear, localized prostate cancer (Gleason score <6), or resected melanoma in situ.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02248805

Contacts
Contact: Joanna Lohr 301-354-3540 lohrj@macrogenics.com
Contact: Susan Brann 301-354-3505 branns@macrogenics.com

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute, Inc Recruiting
Tampa, Florida, United States, 33612
Contact: Tiffany Romershausen, MPH    813-745-2146    Tiffany.Romershausen@moffitt.org   
Principal Investigator: Richard Kim, MD         
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21205
Contact: Ellen Lilly-Foreman, RN, OCN    443-287-4961    lillyel@jhmi.edu   
Contact: Thomas Brown    410-502-5328    tbrown55@jhmi.edu   
Principal Investigator: Daniel Laheru, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Susan Sheehan, RN    617-724-4000    Ssheehan1@mgh.harvard.edu   
Principal Investigator: David P Ryan, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Margaret Carey    617-632-5575    MargaretM_Carey@DFCI.HARVARD.EDU   
Principal Investigator: David P Ryan, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Anthony Amara    919-668-1861    anthony.amara@dm.duke.edu   
Principal Investigator: Herbert Hurwitz, MD         
Carolina Biooncology Institute Recruiting
Huntersville, North Carolina, United States, 28078
Contact: Ashley McClain    704-947-6599 ext 117    amcclain@carolinabiooncology.org   
Principal Investigator: John Powderly, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Yue-yun To, RN    503-215-2855    yue-yun.to@providence.org   
Principal Investigator: Todd Crocenzi, MD         
Sponsors and Collaborators
MacroGenics
Investigators
Study Director: Naimish Pandya, MD MacroGenics
  More Information

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02248805     History of Changes
Other Study ID Numbers: CP-MGD007-01
Study First Received: September 18, 2014
Last Updated: February 8, 2017

Keywords provided by MacroGenics:
colon cancer
colorectal carcinoma
stage IV colorectal cancer

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on June 23, 2017