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

Primary Purpose

Colorectal Carcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MGD007
Sponsored by
MacroGenics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Carcinoma focused on measuring colon cancer, colorectal carcinoma, stage IV colorectal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Yale University, Yale Cancer Center
  • H. Lee Moffitt Cancer Center & Research Institute, Inc
  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Massachusetts General Hospital
  • Dana Farber Cancer Institute
  • Duke University Medical Center
  • Carolina Biooncology Institute
  • Providence Portland Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Does Escalation Arm A

Dose Escalation Arm B

Dose Expansion Arm C

Dose Expansion Arms

Arm Description

MGD007 treatment once weekly

MGD007 treatment once every 3 weeks

MGD007 once every 3 weeks for K-ras wild-type and mutant metastatic CRC

MGD007 2, 3, 6, or 12 doses/cycle

Outcomes

Primary Outcome Measures

Characterize dose limiting toxicity and establish a maximum tolerated dose and schedule
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 MGD007
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
Obtain regular radiographic and clinical evaluations to assess treatment response.

Full Information

First Posted
September 18, 2014
Last Updated
February 4, 2022
Sponsor
MacroGenics
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1. Study Identification

Unique Protocol Identification Number
NCT02248805
Brief Title
Phase 1 Study of MGD007 in Relapsed/Refractory Metastatic Colorectal Carcinoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
October 2014 (Actual)
Primary Completion Date
July 2, 2018 (Actual)
Study Completion Date
July 2, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MacroGenics

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Carcinoma
Keywords
colon cancer, colorectal carcinoma, stage IV colorectal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
95 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Does Escalation Arm A
Arm Type
Experimental
Arm Description
MGD007 treatment once weekly
Arm Title
Dose Escalation Arm B
Arm Type
Experimental
Arm Description
MGD007 treatment once every 3 weeks
Arm Title
Dose Expansion Arm C
Arm Type
Experimental
Arm Description
MGD007 once every 3 weeks for K-ras wild-type and mutant metastatic CRC
Arm Title
Dose Expansion Arms
Arm Type
Experimental
Arm Description
MGD007 2, 3, 6, or 12 doses/cycle
Intervention Type
Drug
Intervention Name(s)
MGD007
Intervention Description
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 Measure Information:
Title
Characterize dose limiting toxicity and establish a maximum tolerated dose and schedule
Description
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.
Time Frame
Cycle 1 of a 6 week cycle
Secondary Outcome Measure Information:
Title
Characterize the PK and Immunogenicity of MGD007
Description
Serum concentrations of MGD007 will be monitored. PK modeling will be performed and an appropriate model will be selected to describe the data.
Time Frame
Beginning of treatment through end of treatment, an expected duration of less than 12 months
Title
Describe any evidence of anti-tumor activity
Description
Obtain regular radiographic and clinical evaluations to assess treatment response.
Time Frame
Every 6 weeks until End of Study, an expected duration of less than 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Yale University, Yale Cancer Center
City
New Haven
State/Province
Connecticut
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute, Inc
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Carolina Biooncology Institute
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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