Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE September 18, 2014
First Posted Date  ICMJE September 25, 2014
Last Update Posted Date August 31, 2018
Actual Study Start Date  ICMJE October 2014
Actual Primary Completion Date July 2, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2014)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02248805 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2017)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2014)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1 Study of MGD007 in Relapsed/Refractory Metastatic Colorectal Carcinoma
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Carcinoma
Intervention  ICMJE 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.
Study Arms  ICMJE
  • Experimental: Does Escalation Arm A
    MGD007 treatment once weekly
    Intervention: Drug: MGD007
  • Experimental: Dose Escalation Arm B
    MGD007 treatment once every 3 weeks
    Intervention: Drug: MGD007
  • Experimental: Dose Expansion Arm C
    MGD007 once every 3 weeks for K-ras wild-type and mutant metastatic CRC
    Intervention: Drug: MGD007
  • Experimental: Dose Expansion Arms
    MGD007 2, 3, 6, or 12 doses/cycle
    Intervention: Drug: MGD007
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 28, 2018)
95
Original Estimated Enrollment  ICMJE
 (submitted: September 22, 2014)
158
Actual Study Completion Date  ICMJE July 2, 2018
Actual Primary Completion Date July 2, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02248805
Other Study ID Numbers  ICMJE CP-MGD007-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MacroGenics
Study Sponsor  ICMJE MacroGenics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jan Davidson-Moncada, MD MacroGenics
PRS Account MacroGenics
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP