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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer
• Intervention / Treatment: Drug: TTX-080; Drug: TTX-080; Drug: pembrolizumab; Drug: cetuximab

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.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale Cancer Center
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Helen F. Graham Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • John Hopkins Kimmer Cancer Center
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Florida Cancer Specialists
    • Fleming Island, Florida, United States, 32003
      • Florida Cancer Specialists
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center
    • Orlando, Florida, United States, 32804
      • AdventHealth Research Institute
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Illinois Cancer Specialists
    • Chicago, Illinois, United States, 60612
      • University of Illinois
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Norton Cancer Institute
  • Maryland
    • Silver Spring, Maryland, United States, 20904
      • Maryland Oncology Hematology
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Center Oncology Hematology West P.C.
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • Stony Brook, New York, United States, 11794
      • Stony Brook University
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Columbus, Ohio, United States, 43219
      • Zangmeister Cancer Center
    • Toledo, Ohio, United States, 43606
      • The University of Toledo
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt - Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Dallas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • Paris, Texas, United States, 75460
      • Texas Oncology - Paris
    • San Antonio, Texas, United States, 78229
      • Next Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Oncology Virginia
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a, Monotherapy Dose Escalation	Drug: TTX-080; Variable dose (Q3W); Drug: TTX-080; Specified 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; Variable dose (Q3W); 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; Variable dose (Q3W); 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; Variable dose (Q3W); 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; Variable dose (Q3W); 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; Variable dose (Q3W); 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; Variable dose (Q3W); 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; Variable dose (Q3W); 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; Variable dose (Q3W); Drug: TTX-080; Specified dose (Q3W); Drug: pembrolizumab; Specified dose (Q3W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Cmax: Maximum Observed Plasma Concentration for TTX-080	Up to 48 months
Tmax: Time to Reach the Cmax for TTX-080	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	Up to 48 months
AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080	Up to 48 months

Collaborators and Investigators

• Sponsor: Tizona Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Cancer; Head and Neck Cancer; Lung Cancer; Gastric Cancer; Prostate Cancer; Pembrolizumab; Melanoma; Cervical Cancer; Colorectal Cancer; Cetuximab; Ovarian Cancer; Antineoplastic Agents; Endometrial Cancer; Triple Negative Breast Cancer; Bladder Cancer; HLA-G; TTX-080; Advanced Solid Tumor; Kidney Cancer; Head and Neck Squamous Cell Carcinoma; Squamous Cell Lung Cancer; Lung Adenocarcinoma; Metastatic Solid Tumor; Renal cell carcinoma; Acral melanoma; Antineoplastic Agents, Immunological
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Cetuximab
• Other Study ID Numbers: TTX-080-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No