History of Changes for Study: NCT04485013

TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers

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Study Record Versions

Version	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:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	TTX-080-001
Brief Title:	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
Secondary IDs:

Study Status


Record Verification:	January 2022
Overall Status:	Recruiting
Study Start:	July 14, 2020
Primary Completion:	December 30, 2022 [Anticipated]
Study Completion:	June 1, 2024 [Anticipated]

First Submitted:	July 15, 2020
First Submitted that Met QC Criteria:	July 21, 2020
First Posted:	July 24, 2020 [Actual]

Last Update Submitted that Met QC Criteria:	January 7, 2022
Last Update Posted:	January 11, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Tizona Therapeutics, Inc
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	No

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.

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.

Conditions


Conditions:	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

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1
Interventional Study Model:	Parallel Assignment
Number of Arms:	9
Masking:	None (Open Label)
Allocation:	Non-Randomized
Enrollment:	200 [Anticipated]

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) 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 MSI-H/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:
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 ]
2.	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 ]
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 ]
5.	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 ]
7.	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 ]
9.	AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080 [ Time Frame: Up to 48 months ]

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
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/Locations


Central Contact Person:	Tizona Therapeutics, Inc. Telephone: 888-585-2990 Email: clinicaltrials@tizonatx.com
Locations:	United States, Connecticut
	Yale Cancer Center [Recruiting] New Haven, Connecticut, United States, 06511 Contact:Contact: Ingrid Palma 203-737-5342 Ingrid.palma@yale.edu
	United States, Florida
	Ocala Oncology Center [Recruiting] Ocala, Florida, United States, 34474 Contact:Contact: Sanjit Nirmalanandhan 352-547-1958 Sanjit.Nirmalanandhan@usoncology.com
	United States, Indiana
	Indiana University [Recruiting] Indianapolis, Indiana, United States, 46202 Contact:Contact: Maria Martinez 317-274-3502 maimarti@iu.edu
	United States, Kentucky
	Norton Cancer Institute [Recruiting] Louisville, Kentucky, United States, 40241 Contact:Contact: Kalyn Weaver Kalyn.Weaver@nortonhealthcare.org
	United States, Massachusetts
	Dana-Farber Cancer Institute [Recruiting] Boston, Massachusetts, United States, 02215 Contact:Contact: Elizabeth Downey 617-582-8705 elizabethe_downey@dfci.harvard.edu
	United States, Michigan
	START Midwest [Recruiting] Grand Rapids, Michigan, United States, 49546 Contact:Contact: Julie Burns, BS 616-954-5559 Julie.burns@startmidwest.com
	United States, Minnesota
	Regions Hospital Cancer Care Center [Recruiting] Saint Paul, Minnesota, United States, 55101 Contact:Contact: Jacquelyn Christenson, BS, LPN 651-254-3602 jacquelyn.christenson@parknicollet.com
	United States, Nebraska
	Nebraska Cancer Center Oncology Hematology West P.C. [Recruiting] Omaha, Nebraska, United States, 68130 Contact:Contact: Megan Meays, M.A. CCRC 402-691-6971 mmeays@nebraskacancer.com
	United States, New Jersey
	Rutgers Cancer Institute of New Jersey [Recruiting] New Brunswick, New Jersey, United States, 08903 Contact:Contact: Elayne Wesolowsky 732-235-3253 wesoloel@cinj.rutgers.edu
	United States, Oklahoma
	University of Oklahoma [Recruiting] Oklahoma City, Oklahoma, United States, 73104 Contact:Contact: Brittany Bell 405-271-8001 Ext. 32084 Brittany-Bell@ouhsc.edu
	United States, Pennsylvania
	University of Pittsburgh Medical Center [Recruiting] Pittsburgh, Pennsylvania, United States, 15232 Contact:Contact: Amy Rose 412-647-8587 kennaj@upmc.edu
	United States, Tennessee
	Sarah Cannon Research Institute [Recruiting] Nashville, Tennessee, United States, 37203 Contact:Contact: Kate Dickinson 615-524-4203 kate.dickinson@sarahcannon.com
	United States, Texas
	The University of Texas MD Anderson Cancer Center [Recruiting] Houston, Texas, United States, 77030 Contact:Contact: Lacey McQuinn lmcquinn@mdanderson.org
	NEXT Oncology [Active, not recruiting] San Antonio, Texas, United States, 78229

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:
Available IPD/Information: