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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04485013
• Other study ID #: TTX-080-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 14, 2020
• Est. completion date: June 1, 2024

Study information

• Verified date: January 2024
• Source: Tizona Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 240
• Est. completion date: June 1, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• TTX-080
Variable dose (Q3W)
• TTX-080
Specified dose (Q3W)
• pembrolizumab
Specified dose (Q3W)
• cetuximab
Specified dose on specified days

Locations

Country	Name	City	State
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Illinois	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Zangmeister Cancer Center	Columbus	Ohio
United States	Texas Oncology - Dallas	Dallas	Texas
United States	Florida Cancer Specialists	Daytona Beach	Florida
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	Florida Cancer Specialists	Fleming Island	Florida
United States	START Midwest	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale Cancer Center	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Christiana Care Helen F. Graham Cancer Center	Newark	Delaware
United States	Hoag Memorial Hospital	Newport Beach	California
United States	Ocala Oncology Center	Ocala	Florida
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Nebraska Cancer Center Oncology Hematology West P.C.	Omaha	Nebraska
United States	AdventHealth Research Institute	Orlando	Florida
United States	Texas Oncology - Paris	Paris	Texas
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Washington University in St Louis	Saint Louis	Missouri
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	NEXT Oncology	San Antonio	Texas
United States	Maryland Oncology Hematology	Silver Spring	Maryland
United States	Stony Brook University	Stony Brook	New York
United States	Northwest Medical Specialties	Tacoma	Washington
United States	The University of Toledo	Toledo	Ohio
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Northwest Cancer Specialists	Vancouver	Washington
United States	John Hopkins Kimmer Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Tizona Therapeutics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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		Up to 48 months
Secondary	Duration of Response, Progression Free Survival per RECIST 1.1		Up to 48 months
Secondary	Overall Survival		Up to 48 months
Secondary	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
Secondary	Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions		Up to 48 months
Secondary	Serum levels of Anti Drug Antibody against TTX-080		Up to 48 months
Secondary	Cmax: Maximum Observed Plasma Concentration for TTX-080		Up to 48 months
Secondary	Tmax: Time to Reach the Cmax for TTX-080		Up to 48 months
Secondary	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
Secondary	AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080		Up to 48 months