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

Sponsor

MacroGenics (Industry)

Overall Status

Completed

CT.gov ID

NCT02248805

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

11.9

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

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 Design

Study Type:

Interventional

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 :

Oct 1, 2014

Actual Primary Completion Date :

Jul 2, 2018

Actual Study Completion Date :

Jul 2, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Characterize dose limiting toxicity and establish a maximum tolerated dose and schedule [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 MGD007 [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University, Yale Cancer Center	New Haven	Connecticut	United States
2	H. Lee Moffitt Cancer Center & Research Institute, Inc	Tampa	Florida	United States	33612
3	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21205
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	Duke University Medical Center	Durham	North Carolina	United States	27710
7	Carolina Biooncology Institute	Huntersville	North Carolina	United States	28078
8	Providence Portland Medical Center	Portland	Oregon	United States	97213