ClinicalTrials.gov
History of Changes for Study: NCT04485013
TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers
Latest version (submitted January 5, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 July 21, 2020 None (earliest Version on record)
2 July 29, 2020 Study Status and Contacts/Locations
3 July 29, 2020 Study Status
4 May 4, 2021 Study Status, Contacts/Locations and Study Design
5 June 30, 2021 Study Status and Contacts/Locations
6 October 11, 2021 Outcome Measures, Arms and Interventions, Study Status, Study Design, Study Description, Eligibility, Conditions and Study Identification
7 December 2, 2021 Study Description, Study Status and Contacts/Locations
8 January 7, 2022 Contacts/Locations and Study Status
9 February 3, 2022 Study Status and Contacts/Locations
10 March 5, 2022 Contacts/Locations and Study Status
11 March 31, 2022 Contacts/Locations and Study Status
12 May 2, 2022 Contacts/Locations and Study Status
13 May 20, 2022 Arms and Interventions and Study Status
14 July 11, 2022 Study Status and Contacts/Locations
15 August 3, 2022 Study Status and Contacts/Locations
16 September 6, 2022 Study Status and Contacts/Locations
17 October 7, 2022 Study Status and Contacts/Locations
18 October 12, 2022 Contacts/Locations and Study Status
19 November 30, 2022 Arms and Interventions, Study Status, Study Description, Eligibility, Outcome Measures, Study Design and Conditions
20 December 2, 2022 Contacts/Locations and Study Status
21 January 26, 2023 Study Status and Conditions
22 February 3, 2023 Study Status and Contacts/Locations
23 June 7, 2023 Contacts/Locations and Study Status
24 July 10, 2023 Recruitment Status, Study Status and Contacts/Locations
25 January 5, 2024 Study Description and Study Status
Comparison Format:
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Changes (Side-by-Side) for Study: NCT04485013
July 10, 2023 (v24) -- January 5, 2024 (v25)

Changes in: Study Status and Study Description
Open or close this module Study Identification
Unique Protocol ID: TTX-080-001 TTX-080-001
Brief Title: TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers
Official Title: A Phase 1a/1b Dose Escalation/Expansion Study of TTX-080, an HLA-G Antagonist, as Monotherapy and in Combination With Pembrolizumab or Cetuximab in Patients With Advanced Solid Refractory/Resistant Malignancies A Phase 1a/1b Dose Escalation/Expansion Study of TTX-080, an HLA-G Antagonist, as Monotherapy and in Combination With Pembrolizumab or Cetuximab in Patients With Advanced Solid Refractory/Resistant Malignancies
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2023 January 2024
Overall Status: Active, not recruitingActive, not recruiting
Study Start: July 14, 2020 July 14, 2020
Primary Completion: December 31, 2023 [Anticipated] December 31, 2023 [Anticipated]
Study Completion: June 1, 2024 [Anticipated] June 1, 2024 [Anticipated]
First Submitted: July 15, 2020 July 15, 2020
First Submitted that
Met QC Criteria:		 July 21, 2020 July 21, 2020
First Posted: July 24, 2020 [Actual] July 24, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:		 July 10, 2023 January 5, 2024
Last Update Posted: July 12, 2023 [Actual] January 9, 2024 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Tizona Therapeutics, Inc Tizona Therapeutics, Inc
Responsible Party: Sponsor Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: YesYes
U.S. FDA-regulated Device: NoNo
Data Monitoring: No No
Open or close this module Study Description
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) or cetuximab (EGFR inhibitor) in patients with advanced refractory / resistant solid malignancies.

The study is enrolling in the dose expansion arms.

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) or cetuximab (EGFR inhibitor) in patients with advanced refractory / resistant solid malignancies.
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 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.

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 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.
Open or close this module Conditions
Conditions: Cancer Cancer
Keywords: HLA-G
TTX-080
Advanced Solid Tumor
Cancer
Ovarian Cancer
Endometrial Cancer
Cervical Cancer
Kidney Cancer
Head and Neck Squamous Cell Carcinoma
Squamous Cell Lung Cancer
Prostate Cancer
Colorectal Cancer
Gastric Cancer
Breast Cancer
Bladder Cancer
Lung Adenocarcinoma
Melanoma
Metastatic Solid Tumor
Renal cell carcinoma
Acral melanoma
Triple Negative Breast Cancer
Pembrolizumab
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Head and Neck Cancer
Lung Cancer 		HLA-G
TTX-080
Advanced Solid Tumor
Cancer
Ovarian Cancer
Endometrial Cancer
Cervical Cancer
Kidney Cancer
Head and Neck Squamous Cell Carcinoma
Squamous Cell Lung Cancer
Prostate Cancer
Colorectal Cancer
Gastric Cancer
Breast Cancer
Bladder Cancer
Lung Adenocarcinoma
Melanoma
Metastatic Solid Tumor
Renal cell carcinoma
Acral melanoma
Triple Negative Breast Cancer
Pembrolizumab
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Head and Neck Cancer
Lung Cancer
Open or close this module Study Design
Study Type: InterventionalInterventional
Primary Purpose: TreatmentTreatment
Study Phase: Phase 1Phase 1
Interventional Study Model: Parallel Assignment Parallel Assignment
Number of Arms: 99
Masking: None (Open Label)None (Open Label)
Allocation: Non-RandomizedNon-Randomized
Enrollment: 240 [Anticipated] 240 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Phase 1a, Monotherapy Dose Escalation Drug: TTX-080
Variable dose (Q3W)
Experimental: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)
Arm 1 will enroll subjects with advanced/metastatic, prior checkpoint inhibitor treated 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)
Arm 2 will enroll subjects with advanced/metastatic 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)
Arm 3 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 cetuximab (CRC), prior anti-EGFR therapy
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
 Drug: TTX-080
Specified dose (Q3W)
Drug: cetuximab
Specified dose on specified days
Experimental: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy
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
 Drug: TTX-080
Specified dose (Q3W)
Drug: cetuximab
Specified dose on specified days
Experimental: Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)
Arm 6 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)
Arm 7 will enroll subjects with advanced/metastatic prior checkpoint inhibitor treated non-small cell lung cancer (NSCLC)
 Drug: TTX-080
Specified dose (Q3W)
Drug: pembrolizumab
Specified dose (Q3W)
Experimental: Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with 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

 Drug: TTX-080
Specified dose (Q3W)
Drug: pembrolizumab
Specified dose (Q3W)
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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 ]

 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 Outcome Measures:
1. Duration of Response, Progression Free Survival per RECIST 1.1
[ Time Frame: Up to 48 months ]

 Duration of Response, Progression Free Survival per RECIST 1.1
[ Time Frame: Up to 48 months ]
2. Overall Survival
[ Time Frame: Up to 48 months ]

 Overall Survival
[ Time Frame: Up to 48 months ]
3. 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 ]

 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 ]
4. Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions
[ 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 ]
5. Serum levels of Anti Drug Antibody against TTX-080
[ Time Frame: Up to 48 months ]

 Serum levels of Anti Drug Antibody against TTX-080
[ Time Frame: Up to 48 months ]
6. Cmax: Maximum Observed Plasma Concentration for TTX-080
[ Time Frame: Up to 48 months ]

 Cmax: Maximum Observed Plasma Concentration for TTX-080
[ Time Frame: Up to 48 months ]
7. Tmax: Time to Reach the Cmax for TTX-080
[ Time Frame: Up to 48 months ]

 Tmax: Time to Reach the Cmax for TTX-080
[ Time Frame: Up to 48 months ]
8. 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-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 ]
9. AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity 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 ]
Open or close this module Eligibility
Minimum Age: 18 Years 18 Years
Maximum Age:
Sex: All All
Gender Based:
Accepts Healthy Volunteers: NoNo
Criteria:

Abbreviated Inclusion Criteria:

  1. Subject with histological diagnosis of advanced/metastatic cancer
  2. Age 18 years or older, is willing and able to provide informed consent
  3. Evidence of measurable disease
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 AND life expectancy of at least 12 weeks

Abbreviated Exclusion Criteria:

  1. History of allergy or hypersensitivity to study treatment components. Subjects with a history of severe hypersensitivity reaction to any monoclonal antibody
  2. Use of an investigational agent within 28 days prior to the first dose of study treatment and throughout the study
  3. Receiving high-dose systemic steroid therapy or any other form of immunosuppressive therapy
  4. History of severe autoimmune disease
  5. Uncontrolled intercurrent illness or other active malignancy requiring ongoing treatment

Abbreviated Inclusion Criteria:

  1. Subject with histological diagnosis of advanced/metastatic cancer
  2. Age 18 years or older, is willing and able to provide informed consent
  3. Evidence of measurable disease
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 AND life expectancy of at least 12 weeks

Abbreviated Exclusion Criteria:

  1. History of allergy or hypersensitivity to study treatment components. Subjects with a history of severe hypersensitivity reaction to any monoclonal antibody
  2. Use of an investigational agent within 28 days prior to the first dose of study treatment and throughout the study
  3. Receiving high-dose systemic steroid therapy or any other form of immunosuppressive therapy
  4. History of severe autoimmune disease
  5. Uncontrolled intercurrent illness or other active malignancy requiring ongoing treatment
Open or close this module Contacts/Locations
Locations: United States, ArizonaUnited States, Arizona
Arizona Oncology Associates
Tucson, Arizona, United States, 85711		Arizona Oncology Associates
Tucson, Arizona, United States, 85711
United States, CaliforniaUnited States, California
University of Southern California
Los Angeles, California, United States, 90033		University of Southern California
Los Angeles, California, United States, 90033
University of California, Los Angeles
Los Angeles, California, United States, 90095		University of California, Los Angeles
Los Angeles, California, United States, 90095
Hoag Memorial Hospital
Newport Beach, California, United States, 92663		Hoag Memorial Hospital
Newport Beach, California, United States, 92663
United States, ColoradoUnited States, Colorado
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218		Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
United States, ConnecticutUnited States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06511		Yale Cancer Center
New Haven, Connecticut, United States, 06511
United States, DelawareUnited States, Delaware
Christiana Care Helen F. Graham Cancer Center
Newark, Delaware, United States, 19713		Christiana Care Helen F. Graham Cancer Center
Newark, Delaware, United States, 19713
United States, District of ColumbiaUnited States, District of Columbia
John Hopkins Kimmer Cancer Center
Washington, District of Columbia, United States, 20016		John Hopkins Kimmer Cancer Center
Washington, District of Columbia, United States, 20016
United States, FloridaUnited States, Florida
Florida Cancer Specialists
Daytona Beach, Florida, United States, 32117		Florida Cancer Specialists
Daytona Beach, Florida, United States, 32117
Florida Cancer Specialists
Fleming Island, Florida, United States, 32003		Florida Cancer Specialists
Fleming Island, Florida, United States, 32003
Ocala Oncology Center
Ocala, Florida, United States, 34474		Ocala Oncology Center
Ocala, Florida, United States, 34474
AdventHealth Research Institute
Orlando, Florida, United States, 32804		AdventHealth Research Institute
Orlando, Florida, United States, 32804
United States, IllinoisUnited States, Illinois
Illinois Cancer Specialists
Arlington Heights, Illinois, United States, 60005		Illinois Cancer Specialists
Arlington Heights, Illinois, United States, 60005
University of Illinois
Chicago, Illinois, United States, 60612		University of Illinois
Chicago, Illinois, United States, 60612
United States, IndianaUnited States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202		Indiana University
Indianapolis, Indiana, United States, 46202
United States, KentuckyUnited States, Kentucky
Norton Cancer Institute
Louisville, Kentucky, United States, 40241		Norton Cancer Institute
Louisville, Kentucky, United States, 40241
United States, MarylandUnited States, Maryland
Maryland Oncology Hematology
Silver Spring, Maryland, United States, 20904		Maryland Oncology Hematology
Silver Spring, Maryland, United States, 20904
United States, MassachusettsUnited States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215		Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, MichiganUnited States, Michigan
START Midwest
Grand Rapids, Michigan, United States, 49546		START Midwest
Grand Rapids, Michigan, United States, 49546
United States, MinnesotaUnited States, Minnesota
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, United States, 55101		Regions Hospital Cancer Care Center
Saint Paul, Minnesota, United States, 55101
United States, MissouriUnited States, Missouri
Washington University in St Louis
Saint Louis, Missouri, United States, 63110		Washington University in St Louis
Saint Louis, Missouri, United States, 63110
United States, NebraskaUnited States, Nebraska
Nebraska Cancer Center Oncology Hematology West P.C.
Omaha, Nebraska, United States, 68130		Nebraska Cancer Center Oncology Hematology West P.C.
Omaha, Nebraska, United States, 68130
United States, New JerseyUnited States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903		Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, New YorkUnited States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029		Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Stony Brook University
Stony Brook, New York, United States, 11794		Stony Brook University
Stony Brook, New York, United States, 11794
United States, OhioUnited States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267		University of Cincinnati
Cincinnati, Ohio, United States, 45267
Zangmeister Cancer Center
Columbus, Ohio, United States, 43219		Zangmeister Cancer Center
Columbus, Ohio, United States, 43219
The University of Toledo
Toledo, Ohio, United States, 43606		The University of Toledo
Toledo, Ohio, United States, 43606
United States, OklahomaUnited States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104		University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, PennsylvaniaUnited States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232		University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232
United States, South CarolinaUnited States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425		Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, TennesseeUnited States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203		Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, United States, 37232		Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, TexasUnited States, Texas
Texas Oncology - Dallas
Dallas, Texas, United States, 75246		Texas Oncology - Dallas
Dallas, Texas, United States, 75246
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030		The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Texas Oncology - Paris
Paris, Texas, United States, 75460		Texas Oncology - Paris
Paris, Texas, United States, 75460
NEXT Oncology
San Antonio, Texas, United States, 78229		NEXT Oncology
San Antonio, Texas, United States, 78229
United States, VirginiaUnited States, Virginia
NEXT Oncology Virginia
Fairfax, Virginia, United States, 22031		NEXT Oncology Virginia
Fairfax, Virginia, United States, 22031
United States, WashingtonUnited States, Washington
Northwest Medical Specialties
Tacoma, Washington, United States, 98405		Northwest Medical Specialties
Tacoma, Washington, United States, 98405
Northwest Cancer Specialists
Vancouver, Washington, United States, 98684		Northwest Cancer Specialists
Vancouver, Washington, United States, 98684
Open or close this module IPDSharing
Plan to Share IPD: No No
Open or close this module References
Citations:
Links:
Available IPD/Information:
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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services