Clinical trial NCT04485013: 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, Cetuximab or FOLFIRI Plus Cetuximab in Patients With Advanced Solid Refractory/Resistant Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Renal cell carcinoma
Acral melanoma
Triple Negative Breast Cancer
Pembrolizumab
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Head and Neck Cancer
Lung Cancer
Lead sponsor: Tizona Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2020-07-24
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Up to 48 months
Secondary outcomes:
measure: Duration of Response, Progression Free Survival per RECIST 1.1
timeFrame: Up to 48 months
measure: Overall Survival
timeFrame: Up to 48 months
measure: 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
timeFrame: Up to 48 months
measure: Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions
timeFrame: Up to 48 months
measure: Serum levels of Anti Drug Antibody against TTX-080
timeFrame: Up to 48 months
measure: Cmax: Maximum Observed Plasma Concentration for TTX-080
timeFrame: Up to 48 months
measure: Tmax: Time to Reach the Cmax for TTX-080
timeFrame: Up to 48 months
measure: AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for TTX-080
timeFrame: Up to 48 months
measure: AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080
timeFrame: Up to 48 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Helen F. Graham Cancer Center
state: Delaware
city: Washington
country: United States
facility: John Hopkins Kimmer Cancer Center
state: District of Columbia
city: Daytona Beach
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Fleming Island
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Research Institute
state: Florida
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Center Oncology Hematology West P.C.
state: Nebraska
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Zangmeister Cancer Center
state: Ohio
city: Toledo
country: United States
facility: The University of Toledo
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Dallas
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Paris
country: United States
facility: Texas Oncology - Paris
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists
state: Washington
Study officials:
References: