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

NCT02248805 | Completed Phase 1

• 1 other identifier: CP-MGD007-01
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 8

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.

Conditions

Colorectal Carcinoma

Keywords

colon cancer; colorectal carcinoma; stage IV colorectal cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Cycle 1 of a 6 week cycle

Secondary Outcomes (2)

• Characterize the PK and Immunogenicity of MGD007

  Beginning of treatment through end of treatment, an expected duration of less than 12 months

• Describe any evidence of anti-tumor activity

  Every 6 weeks until End of Study, an expected duration of less than 12 months

Study Arms (4)

Does Escalation Arm A

EXPERIMENTAL

MGD007 treatment once weekly

Drug: MGD007

Dose Escalation Arm B

EXPERIMENTAL

MGD007 treatment once every 3 weeks

Drug: MGD007

Dose Expansion Arm C

EXPERIMENTAL

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

Drug: MGD007

Dose Expansion Arms

EXPERIMENTAL

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

Drug: MGD007

Interventions

MGD007 DRUG

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.

Does Escalation Arm A; Dose Escalation Arm B; Dose Expansion Arm C; Dose Expansion Arms

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• MacroGenics: lead

Study Sites (8)

Yale University, Yale Cancer Center

New Haven, Connecticut, United States

Location

H. Lee Moffitt Cancer Center & Research Institute, Inc

Tampa, Florida, 33612, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Carolina Biooncology Institute

Huntersville, North Carolina, 28078, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2014
• First Posted: September 25, 2014
• Study Start: October 1, 2014
• Primary Completion: July 2, 2018
• Study Completion: July 2, 2018
• Last Updated: February 8, 2022

Record last verified: 2022-02

Locations

US (8)