Clinical trial NCT02248805: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Carcinoma
Keywords: colon cancer
colorectal carcinoma
stage IV colorectal cancer
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2014-09-25
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Characterize dose limiting toxicity and establish a maximum tolerated dose and schedule
timeFrame: Cycle 1 of a 6 week cycle
Secondary outcomes:
measure: Characterize the PK and Immunogenicity of MGD007
timeFrame: Beginning of treatment through end of treatment, an expected duration of less than 12 months
measure: Describe any evidence of anti-tumor activity
timeFrame: Every 6 weeks until End of Study, an expected duration of less than 12 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University, Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute, Inc
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Huntersville
country: United States
facility: Carolina Biooncology Institute
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
Study officials:
References: