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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04485013
Recruitment Status : Recruiting
First Posted : July 24, 2020
Last Update Posted : May 26, 2022
Sponsor:
Information provided by (Responsible Party):
Tizona Therapeutics, Inc

Study Description
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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.


Condition or disease Intervention/treatment Phase
Cancer Drug: TTX-080 Drug: pembrolizumab Drug: cetuximab Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 14, 2020
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : June 1, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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 MSS/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
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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 Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04485013


Contacts
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Contact: Tizona Therapeutics, Inc. 888-585-2990 clinicaltrials@tizonatx.com

Locations
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Sponsors and Collaborators
Tizona Therapeutics, Inc
More Information
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Responsible Party: Tizona Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT04485013    
Other Study ID Numbers: TTX-080-001
First Posted: July 24, 2020    Key Record Dates
Last Update Posted: May 26, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tizona Therapeutics, Inc:
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
Additional relevant MeSH terms:
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Pembrolizumab
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents