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

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ClinicalTrials.gov Identifier: NCT02248805
Recruitment Status : Completed
First Posted : September 25, 2014
Last Update Posted : August 31, 2018
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Brief Summary:
The primary goal of this Phase 1 study is to characterize the safety and tolerability of MGD007 and establish the maximum tolerated dose (MTD) and schedule of MGD007 administered to patients with metastatic colorectal carcinoma. Pharmacokinetics, pharmacodynamics, and the anti-tumor activity of MGD007 will also be assessed.

Condition or disease Intervention/treatment Phase
Colorectal Carcinoma Drug: MGD007 Phase 1

Detailed Description:

This is an 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 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 four separate dose expansion cohorts to further optimize the dose and schedule of MGD007 administration.

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, First-in-Human, Open Label, Dose Escalation Study of MGD007, A Humanized gpA33 x CD3 DART® Protein in Patients With Relapsed/Refractory Metastatic Colorectal Carcinoma
Actual Study Start Date : October 2014
Actual Primary Completion Date : July 2, 2018
Actual Study Completion Date : July 2, 2018

Arm Intervention/treatment
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 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 DART molecule. MGD007 will be administered as a single agent.

Experimental: Dose Expansion Arm C
MGD007 once every 3 weeks for K-ras wild-type and mutant metastatic CRC
Drug: MGD007
MGD007 is a gpA33 x CD3 bi-specific antibody-based molecular construct referred to as a DART molecule. MGD007 will be administered as a single agent.

Experimental: Dose Expansion Arms
MGD007 2, 3, 6, or 12 doses/cycle
Drug: MGD007
MGD007 is a gpA33 x CD3 bi-specific antibody-based molecular construct referred to as a DART molecule. MGD007 will be administered as a single agent.




Primary Outcome Measures :
  1. 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 :
  1. Characterize the PK and Immunogenicity of MGD007 [ 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.

  2. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02248805


Locations
United States, Connecticut
Yale University, Yale Cancer Center
New Haven, Connecticut, United States
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute, Inc
Tampa, Florida, United States, 33612
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Carolina Biooncology Institute
Huntersville, North Carolina, United States, 28078
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
Sponsors and Collaborators
MacroGenics
Investigators
Study Director: Jan Davidson-Moncada, MD MacroGenics

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT02248805     History of Changes
Other Study ID Numbers: CP-MGD007-01
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018

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