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

NCT04485013 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TTX-080-001
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 41

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.

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

Outcome Measures

Primary Outcomes (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

  Up to 48 months

Secondary Outcomes (9)

• 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

Study Arms (11)

Phase 1a, Monotherapy Dose Escalation

EXPERIMENTAL

Drug: TTX-080

Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)

EXPERIMENTAL

Arm 1 will enroll subjects with advanced/metastatic, prior checkpoint inhibitor treated Head and Neck Squamous Cell Carcinoma (HNSCC) \[Closed\]

Drug: TTX-080; Drug: pembrolizumab

Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)

EXPERIMENTAL

Arm 2 will enroll subjects with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) \[Closed\]

Drug: TTX-080; Drug: cetuximab

Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC)

EXPERIMENTAL

Arm 3 will enroll subjects with advanced/metastatic colorectal cancer (CRC) \[Closed\]

Drug: TTX-080

Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy

EXPERIMENTAL

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 \[Closed\]

Drug: TTX-080; Drug: cetuximab

Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy

EXPERIMENTAL

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 \[Closed\]

Drug: TTX-080; Drug: cetuximab

Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)

EXPERIMENTAL

Arm 6 will enroll subjects with advanced/metastatic non-small cell lung cancer (NSCLC) \[Closed\]

Drug: TTX-080

Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)

EXPERIMENTAL

Arm 7 will enroll subjects with advanced/metastatic prior checkpoint inhibitor treated non-small cell lung cancer (NSCLC) \[Closed\]

Drug: TTX-080; Drug: pembrolizumab

Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab

EXPERIMENTAL

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 \[Closed\]

Drug: TTX-080; Drug: pembrolizumab

TTX-080 in combination with FOLFIRI plus cetuximab

EXPERIMENTAL

Arm 9: TTX-080 in combination with FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor.

Drug: FOLFIRI; Drug: cetuximab; Drug: TTX-080

FOLFIRI plus cetuximab

EXPERIMENTAL

Arm 10: FOLFIRI plus cetuximab Randomized Arms in subjects with metastatic RAS, BRAF and HER2 wild type colorectal cancer (CRC) who have been received oxaliplatin and 5-FU based chemotherapy in the first line or adjuvant (relapse within 6 months) setting. Prior bevacizumab allowed. No prior EGFR inhibitor.

Drug: FOLFIRI; Drug: cetuximab

Interventions

TTX-080 DRUG

Variable dose (Q3W)

Phase 1a, Monotherapy Dose Escalation

pembrolizumab DRUG

Specified dose (Q3W)

Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab; Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC); Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)

cetuximab DRUG

Specified dose on specified days

Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy; Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy; Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)

FOLFIRI DRUG

Specified dose (Q2W)

FOLFIRI plus cetuximab; TTX-080 in combination with FOLFIRI plus cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject with histological diagnosis of advanced/metastatic cancer \[currently enrolling in CRC only\]
• 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 AND life expectancy of at least 12 weeks

You may not qualify if:

• 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

Sponsors & Collaborators

• Tizona Therapeutics, Inc: lead

Study Sites (41)

Arizona Oncology Associates

Tucson, Arizona, 85711, United States

COMPLETED

University of Southern California

Los Angeles, California, 90033, United States

COMPLETED

Hoag Memorial Hospital

Newport Beach, California, 92663, United States

COMPLETED

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06511, United States

COMPLETED

Christiana Care Helen F. Graham Cancer Center

Newark, Delaware, 19713, United States

COMPLETED

John Hopkins Kimmer Cancer Center

Washington D.C., District of Columbia, 20016, United States

COMPLETED

Florida Cancer Specialists

Daytona Beach, Florida, 32117, United States

RECRUITING

Florida Cancer Specialists

Fleming Island, Florida, 32003, United States

COMPLETED

Ocala Oncology Center

Ocala, Florida, 34474, United States

RECRUITING

AdventHealth Research Institute

Orlando, Florida, 32804, United States

COMPLETED

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

COMPLETED

University of Illinois

Chicago, Illinois, 60612, United States

COMPLETED

Indiana University

Indianapolis, Indiana, 46202, United States

COMPLETED

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

COMPLETED

American Oncology Partners, P.A. - The Center for Cancer & Blood Disorders

Bethesda, Maryland, 20817, United States

RECRUITING

Maryland Oncology Hematology

Silver Spring, Maryland, 20904, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

COMPLETED

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, 55101, United States

RECRUITING

Washington University in St Louis

St Louis, Missouri, 63110, United States

COMPLETED

Nebraska Cancer Center Oncology Hematology West P.C.

Omaha, Nebraska, 68130, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

COMPLETED

Stony Brook University

Stony Brook, New York, 11794, United States

COMPLETED

University of Cincinnati

Cincinnati, Ohio, 45267, United States

RECRUITING

Zangmeister Cancer Center

Columbus, Ohio, 43219, United States

COMPLETED

The University of Toledo

Toledo, Ohio, 43606, United States

COMPLETED

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

COMPLETED

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

COMPLETED

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, 37232, United States

COMPLETED

Texas Oncology - Dallas

Dallas, Texas, 75246, United States

RECRUITING

START Dallas

Fort Worth, Texas, 76104, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

COMPLETED

Texas Oncology - Paris

Paris, Texas, 75460, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

COMPLETED

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

COMPLETED

Northwest Cancer Specialists

Vancouver, Washington, 98684, United States

COMPLETED

MeSH Terms

Conditions

Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms; Uterine Cervical Neoplasms; Kidney Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prostatic Neoplasms; Colorectal Neoplasms; Stomach Neoplasms; Breast Neoplasms; Urinary Bladder Neoplasms; Adenocarcinoma of Lung; Melanoma; Neoplasm Metastasis; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms; Head and Neck Neoplasms; Lung Neoplasms

Interventions

pembrolizumab; Cetuximab; IFL protocol

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Uterine Cervical Diseases; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Urinary Bladder Diseases; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Tizona Therapeutics, Inc.

CONTACT

888-585-2990; clinicaltrials@tizonatx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2020
• First Posted: July 24, 2020
• Study Start: July 14, 2020
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 18, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (41)