Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
CP-MGD007-01
- NCT ID:
NCT02248805
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| MGD007 | | Does Escalation Arm A |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Does Escalation Arm A | Experimental | MGD007 treatment once weekly | |
| Dose Escalation Arm B | Experimental | MGD007 treatment once every 3 weeks | |
| Dose Expansion Arm C | Experimental | MGD007 once every 3 weeks for K-ras wild-type and mutant metastatic CRC | |
| Dose Expansion Arms | Experimental | MGD007 2, 3, 6, or 12 doses/cycle | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Characterize dose limiting toxicity and establish a maximum tolerated dose and schedule |
| Time Frame: | Cycle 1 of a 6 week cycle |
| Safety Issue: | |
| 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. |
Secondary Outcome Measures
| Measure: | Characterize the PK and Immunogenicity of MGD007 |
| Time Frame: | Beginning of treatment through end of treatment, an expected duration of less than 12 months |
| Safety Issue: | |
| Description: | Serum concentrations of MGD007 will be monitored. PK modeling will be performed and an appropriate model will be selected to describe the data. |
| Measure: | Describe any evidence of anti-tumor activity |
| Time Frame: | Every 6 weeks until End of Study, an expected duration of less than 12 months |
| Safety Issue: | |
| Description: | Obtain regular radiographic and clinical evaluations to assess treatment response. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | MacroGenics |
Trial Keywords
- colon cancer
- colorectal carcinoma
- stage IV colorectal cancer
Last Updated
August 31, 2018
