TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers
- Conditions
- Cancer
- Interventions
- Registration Number
- NCT04485013
- Lead Sponsor
- Tizona Therapeutics, Inc
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 240
- Subject with histological diagnosis of advanced/metastatic cancer
- Age 18 years or older, is willing and able to provide informed consent
- Evidence of measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 AND life expectancy of at least 12 weeks
Abbreviated
- History of allergy or hypersensitivity to study treatment components. Subjects with a history of severe hypersensitivity reaction to any monoclonal antibody
- Use of an investigational agent within 28 days prior to the first dose of study treatment and throughout the study
- Receiving high-dose systemic steroid therapy or any other form of immunosuppressive therapy
- History of severe autoimmune disease
- Uncontrolled intercurrent illness or other active malignancy requiring ongoing treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC) pembrolizumab Arm 1 will enroll subjects with advanced/metastatic, prior checkpoint inhibitor treated Head and Neck Squamous Cell Carcinoma (HNSCC) Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC) cetuximab Arm 2 will enroll subjects with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC) TTX-080 Arm 3 will enroll subjects with advanced/metastatic colorectal cancer (CRC) Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy cetuximab Arm 4 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild-type colorectal cancer (CRC) who have progressed on a prior anti-EGFR therapy Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy TTX-080 Arm 5 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild type colorectal cancer (CRC) who have not received a prior anti-EGFR therapy Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy cetuximab Arm 5 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild type colorectal cancer (CRC) who have not received a prior anti-EGFR therapy Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC) TTX-080 Arm 7 will enroll subjects with advanced/metastatic prior checkpoint inhibitor treated non-small cell lung cancer (NSCLC) Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC) pembrolizumab Arm 7 will enroll subjects with advanced/metastatic prior checkpoint inhibitor treated non-small cell lung cancer (NSCLC) Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab pembrolizumab Arm 8: TTX-080 monotherapy: * Advanced/metastatic, prior checkpoint inhibitor treated renal cell carcinoma with predominance of clear cell component * Advanced/metastatic acral melanoma Arm 8: TTX-080 in combination with pembrolizumab: • Advanced/metastatic triple-negative breast cancer (estrogen and progesterone receptor negative and HER2 negative) who has received a prior checkpoint inhibitor TTX-080 in combination with FOLFIRI plus cetuximab FOLFIRI Arm 9: TTX-080 in combination with FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor. TTX-080 in combination with FOLFIRI plus cetuximab cetuximab Arm 9: TTX-080 in combination with FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor. FOLFIRI plus cetuximab FOLFIRI Arm 10: FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor. FOLFIRI plus cetuximab cetuximab Arm 10: FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor. Phase 1a, Monotherapy Dose Escalation TTX-080 - Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC) TTX-080 Arm 6 will enroll subjects with advanced/metastatic non-small cell lung cancer (NSCLC) TTX-080 in combination with FOLFIRI plus cetuximab TTX-080 Arm 9: TTX-080 in combination with FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor. Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC) TTX-080 Arm 1 will enroll subjects with advanced/metastatic, prior checkpoint inhibitor treated Head and Neck Squamous Cell Carcinoma (HNSCC) Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC) TTX-080 Arm 2 will enroll subjects with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy TTX-080 Arm 4 will enroll subjects with advanced/metastatic MSI-L/MSS, KRAS wild-type colorectal cancer (CRC) who have progressed on a prior anti-EGFR therapy Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab TTX-080 Arm 8: TTX-080 monotherapy: * Advanced/metastatic, prior checkpoint inhibitor treated renal cell carcinoma with predominance of clear cell component * Advanced/metastatic acral melanoma Arm 8: TTX-080 in combination with pembrolizumab: • Advanced/metastatic triple-negative breast cancer (estrogen and progesterone receptor negative and HER2 negative) who has received a prior checkpoint inhibitor
- Primary Outcome Measures
Name Time Method 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 Up to 48 months
- Secondary Outcome Measures
Name Time Method Duration of Response, Progression Free Survival per RECIST 1.1 Up to 48 months Overall Survival Up to 48 months Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions Up to 48 months Serum levels of Anti Drug Antibody against TTX-080 Up to 48 months Cmax: Maximum Observed Plasma Concentration for TTX-080 Up to 48 months Tmax: Time to Reach the Cmax for TTX-080 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 Up to 48 months AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080 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 Up to 48 months
Trial Locations
- Locations (38)
Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Hoag Memorial Hospital
🇺🇸Newport Beach, California, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Christiana Care Helen F. Graham Cancer Center
🇺🇸Newark, Delaware, United States
John Hopkins Kimmer Cancer Center
🇺🇸Washington, District of Columbia, United States
Florida Cancer Specialists
🇺🇸Fleming Island, Florida, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
AdventHealth Research Institute
🇺🇸Orlando, Florida, United States
Illinois Cancer Specialists
🇺🇸Arlington Heights, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Maryland Oncology Hematology
🇺🇸Silver Spring, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Regions Hospital Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
Washington University in St Louis
🇺🇸Saint Louis, Missouri, United States
Nebraska Cancer Center Oncology Hematology West P.C.
🇺🇸Omaha, Nebraska, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Stony Brook University
🇺🇸Stony Brook, New York, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Zangmeister Cancer Center
🇺🇸Columbus, Ohio, United States
The University of Toledo
🇺🇸Toledo, Ohio, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Vanderbilt - Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Texas Oncology - Dallas
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Texas Oncology - Paris
🇺🇸Paris, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
NEXT Oncology Virginia
🇺🇸Fairfax, Virginia, United States
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
Northwest Cancer Specialists
🇺🇸Vancouver, Washington, United States