TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers
Study Details
Study Description
Brief Summary
TTX-080-01 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) or cetuximab (EGFR inhibitor) in patients with advanced refractory / resistant solid malignancies.
The study is enrolling in the dose expansion cohorts.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
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), and triple negative breast cancer (TNBC). Additionally, the study will seek to evaluate the pharmacokinetics and immunogenicity of TTX-080, and preliminary efficacy of TTX-080 as a monotherapy and in combination with pembrolizumab or cetuximab.
The study is enrolling in the dose expansion cohorts.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Phase 1a, Monotherapy Dose Escalation
|
Drug: TTX-080
Variable dose (Q3W)
|
Experimental: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC) Cohorts will enroll subjects with advanced/metastatic PD-1/PD-L1 experienced Head and Neck Squamous Cell Carcinoma (HNSCC) |
Drug: TTX-080
Specified dose (Q3W)
Drug: pembrolizumab
Specified dose (Q3W)
|
Experimental: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC) Cohorts will enroll subjects with advanced/metastatic PD-1/PD-L1 experienced Head and Neck Squamous Cell Carcinoma (HNSCC) |
Drug: TTX-080
Specified dose (Q3W)
Drug: cetuximab
Specified dose on specified days
|
Experimental: Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC) Cohorts will enroll subjects with advanced/metastatic colorectal cancer (CRC) |
Drug: TTX-080
Specified dose (Q3W)
|
Experimental: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (CRC) Cohorts will enroll subjects with advanced/metastatic MSI-H/dMMR colorectal cancer (CRC) |
Drug: TTX-080
Specified dose (Q3W)
Drug: pembrolizumab
Specified dose (Q3W)
|
Experimental: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC) Cohorts will enroll subjects with advanced/metastatic MSS/dMMR (KRAS wild type) colorectal cancer (CRC) |
Drug: TTX-080
Specified dose (Q3W)
Drug: cetuximab
Specified dose on specified days
|
Experimental: Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC) Cohorts will enroll subjects with advanced/metastatic non-small cell lung cancer (NSCLC) |
Drug: TTX-080
Specified dose (Q3W)
|
Experimental: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC) Cohorts will enroll subjects with advanced/metastatic non-small cell lung cancer (NSCLC) |
Drug: TTX-080
Specified dose (Q3W)
Drug: pembrolizumab
Specified dose (Q3W)
|
Experimental: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (TNBC) Cohorts will enroll subjects with advanced/metastatic triple negative breast cancer (TNBC) |
Drug: TTX-080
Specified dose (Q3W)
Drug: pembrolizumab
Specified dose (Q3W)
|
Outcome Measures
Primary Outcome Measures
- 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
- Duration of Response, Progression Free Survival per RECIST 1.1 [Up to 48 months]
- Overall Survival [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]
- 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]
Eligibility Criteria
Criteria
Abbreviated Inclusion Criteria:
-
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
Abbreviated Exclusion Criteria:
-
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Arizona Oncology Associates | Tucson | Arizona | United States | 85711 |
2 | University of Southern California | Los Angeles | California | United States | 90033 |
3 | University of California, Los Angeles | Los Angeles | California | United States | 90095 |
4 | Hoag Memorial Hospital | Newport Beach | California | United States | 92663 |
5 | Yale Cancer Center | New Haven | Connecticut | United States | 06511 |
6 | Christiana Care Helen F. Graham Cancer Center | Newark | Delaware | United States | 19713 |
7 | John Hopkins Kimmer Cancer Center | Washington | District of Columbia | United States | 20016 |
8 | Florida Cancer Specialists | Daytona Beach | Florida | United States | 32117 |
9 | Florida Cancer Specialists | Fleming Island | Florida | United States | 32003 |
10 | Ocala Oncology Center | Ocala | Florida | United States | 34474 |
11 | AdventHealth Research Institute | Orlando | Florida | United States | 32804 |
12 | Illinois Cancer Specialists | Arlington Heights | Illinois | United States | 60005 |
13 | University of Illinois | Chicago | Illinois | United States | 60612 |
14 | Indiana University | Indianapolis | Indiana | United States | 46202 |
15 | Norton Cancer Institute | Louisville | Kentucky | United States | 40241 |
16 | Maryland Oncology Hematology | Silver Spring | Maryland | United States | 20904 |
17 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
18 | START Midwest | Grand Rapids | Michigan | United States | 49546 |
19 | Regions Hospital Cancer Care Center | Saint Paul | Minnesota | United States | 55101 |
20 | Washington University in St Louis | Saint Louis | Missouri | United States | 63110 |
21 | Nebraska Cancer Center Oncology Hematology West P.C. | Omaha | Nebraska | United States | 68130 |
22 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08903 |
23 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
24 | Zangmeister Cancer Center | Columbus | Ohio | United States | 43219 |
25 | The University of Toledo | Toledo | Ohio | United States | 43606 |
26 | University of Oklahoma | Oklahoma City | Oklahoma | United States | 73104 |
27 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15232 |
28 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
29 | Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
30 | Vanderbilt - Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
31 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
32 | Texas Oncology - Paris | Paris | Texas | United States | 75460 |
33 | NEXT Oncology | San Antonio | Texas | United States | 78229 |
34 | Northwest Cancer Specialists | Vancouver | Washington | United States | 98684 |
Sponsors and Collaborators
- Tizona Therapeutics, Inc
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TTX-080-001