A Phase 1a/1b Dose Escalation/Expansion Study of TTX-080, an HLA-G Antagonist, as Monotherapy and in Combination With Pembrolizumab, Cetuximab or FOLFIRI Plus Cetuximab in Patients With Advanced Solid Refractory/Resistant Malignancies
Summary
TTX-080-001 is a Phase 1, open label, dose escalation and dose expansion clinical study to determine the safety, tolerability, and recommended Phase 2 dose of TTX-080 monotherapy (HLA-G inhibitor) and in combination with either pembrolizumab (PD-1 inhibitor), cetuximab (EGFR inhibitor) or FOLFIRI plus cetuximab (EGFR inhibitor) in patients with advanced refractory / resistant solid malignancies including metastatic colorectal cancer (mCRC) patients.
Detailed description
TTX-080 is a fully human mAb designed to block the interaction of HLA-G with its known ligands, ILT2 and ILT4 molecules. The Phase 1a was an open label, multicenter, dose escalation clinical trial to determine the safety, tolerability, MTD or OBD, and the RP2D of TTX-080 when administered as a single agent. The Phase 1b is a dose expansion of TTX-080 monotherapy and in combination with either pembrolizumab or cetuximab in adult subjects with advanced refractory/resistant solid malignancies, including Head and Neck squamous cell carcinoma (HNSCC), Non-Small Cell Lung Cancer (NSCLC), Colorectal cancer (CRC), triple negative breast cancer (TNBC), renal cell carcinoma (RCC), and acral melanoma. Additionally, the Phase 1b includes randomized arms with TTX-080 in combination with FOLFIRI plus cetuximab compared to FOLFIRI plus cetuximab in metastatic Colorectal cancer. The study will seek to evaluate the pharmacokinetics and immunogenicity of TTX-080, and characterize the anti-tumor activity of TTX-080 as a monotherapy and in combination with pembrolizumab, cetuximab or FOLFIRI plus cetuximab. Only arm 9 and 10 are currently open to enrollment.
Arms & interventions
- DrugTTX-080
Variable dose (Q3W)
- DrugTTX-080
Specified dose (Q3W)
- Drugpembrolizumab
Specified dose (Q3W)
- Drugcetuximab
Specified dose on specified days
- DrugFOLFIRI
Specified dose (Q2W)
- Drugcetuximab
Specified dose (Q2W)
- DrugTTX-080
Specified dose (Q2W)
Outcome measures
Primary
1. To determine the anti-tumor activity of TTX-080 by objective response rate [complete response + partial response) for each tumor arm per RECIST 1.1
Time frame: Up to 48 months
Secondary
Duration of Response, Progression Free Survival per RECIST 1.1
Time frame: Up to 48 months
Overall Survival
Time frame: Up to 48 months
Adverse events (AEs) as characterized by the incidence, type, frequency, severity (graded according to NCI-CTCAE v5.0), timing, seriousness, and relationship to investigational product, and/or combination therapy, and/or individual approved therapies
Time frame: Up to 48 months
Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions
Time frame: Up to 48 months
Serum levels of Anti Drug Antibody against TTX-080
Time frame: Up to 48 months
Cmax: Maximum Observed Plasma Concentration for TTX-080
Time frame: Up to 48 months
Tmax: Time to Reach the Cmax for TTX-080
Time frame: Up to 48 months
AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for TTX-080
Time frame: Up to 48 months
AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080
Time frame: Up to 48 months
Eligibility criteria
Study locations (41)
Arizona Oncology Associates
Tucson, Arizona, 85711
University of Southern California
Los Angeles, California, 90033
Hoag Memorial Hospital
Newport Beach, California, 92663
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Yale Cancer Center
New Haven, Connecticut, 06511
Christiana Care Helen F. Graham Cancer Center
Newark, Delaware, 19713
John Hopkins Kimmer Cancer Center
Washington D.C., District of Columbia, 20016
Florida Cancer Specialists
Daytona Beach, Florida, 32117
Florida Cancer Specialists
Fleming Island, Florida, 32003
Ocala Oncology Center
Ocala, Florida, 34474
AdventHealth Research Institute
Orlando, Florida, 32804
Illinois Cancer Specialists
Arlington Heights, Illinois, 60005
University of Illinois
Chicago, Illinois, 60612
Indiana University
Indianapolis, Indiana, 46202
Norton Cancer Institute
Louisville, Kentucky, 40241
American Oncology Partners, P.A. - The Center for Cancer & Blood Disorders
Bethesda, Maryland, 20817
Maryland Oncology Hematology
Silver Spring, Maryland, 20904
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
START Midwest
Grand Rapids, Michigan, 49546
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, 55101
Washington University in St Louis
St Louis, Missouri, 63110
Nebraska Cancer Center Oncology Hematology West P.C.
Omaha, Nebraska, 68130
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Stony Brook University
Stony Brook, New York, 11794
University of Cincinnati
Cincinnati, Ohio, 45267
Zangmeister Cancer Center
Columbus, Ohio, 43219
The University of Toledo
Toledo, Ohio, 43606
University of Oklahoma
Oklahoma City, Oklahoma, 73104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
Medical University of South Carolina
Charleston, South Carolina, 29425
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, 37232
Texas Oncology - Dallas
Dallas, Texas, 75246
START Dallas
Fort Worth, Texas, 76104
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Texas Oncology - Paris
Paris, Texas, 75460
NEXT Oncology
San Antonio, Texas, 78229
NEXT Oncology Virginia
Fairfax, Virginia, 22031
Northwest Medical Specialties
Tacoma, Washington, 98405
Northwest Cancer Specialists
Vancouver, Washington, 98684