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

Sponsor
Tizona Therapeutics, Inc (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04485013
Collaborator
(none)
200
34
9
46.6
5.9
0.1

Study Details

Study Description

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
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

Study Type:
Interventional
Anticipated 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 :
Jul 14, 2020
Anticipated Primary Completion Date :
Dec 30, 2022
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

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

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 [Up to 48 months]

Secondary Outcome Measures

  1. Duration of Response, Progression Free Survival per RECIST 1.1 [Up to 48 months]

  2. Overall Survival [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 [Up to 48 months]

  4. Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions [Up to 48 months]

  5. Serum levels of Anti Drug Antibody against TTX-080 [Up to 48 months]

  6. Cmax: Maximum Observed Plasma Concentration for TTX-080 [Up to 48 months]

  7. Tmax: Time to Reach the Cmax for TTX-080 [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 [Up to 48 months]

  9. AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080 [Up to 48 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 Arizona Oncology Associates Tucson Arizona United States 85711
2 University of Southern California Los Angeles California United States 90033
3 University of California, Los Angeles Los Angeles California United States 90095
4 Hoag Memorial Hospital Newport Beach California United States 92663
5 Yale Cancer Center New Haven Connecticut United States 06511
6 Christiana Care Helen F. Graham Cancer Center Newark Delaware United States 19713
7 John Hopkins Kimmer Cancer Center Washington District of Columbia United States 20016
8 Florida Cancer Specialists Daytona Beach Florida United States 32117
9 Florida Cancer Specialists Fleming Island Florida United States 32003
10 Ocala Oncology Center Ocala Florida United States 34474
11 AdventHealth Research Institute Orlando Florida United States 32804
12 Illinois Cancer Specialists Arlington Heights Illinois United States 60005
13 University of Illinois Chicago Illinois United States 60612
14 Indiana University Indianapolis Indiana United States 46202
15 Norton Cancer Institute Louisville Kentucky United States 40241
16 Maryland Oncology Hematology Silver Spring Maryland United States 20904
17 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
18 START Midwest Grand Rapids Michigan United States 49546
19 Regions Hospital Cancer Care Center Saint Paul Minnesota United States 55101
20 Washington University in St Louis Saint Louis Missouri United States 63110
21 Nebraska Cancer Center Oncology Hematology West P.C. Omaha Nebraska United States 68130
22 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
23 Icahn School of Medicine at Mount Sinai New York New York United States 10029
24 Zangmeister Cancer Center Columbus Ohio United States 43219
25 The University of Toledo Toledo Ohio United States 43606
26 University of Oklahoma Oklahoma City Oklahoma United States 73104
27 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15232
28 Medical University of South Carolina Charleston South Carolina United States 29425
29 Sarah Cannon Research Institute Nashville Tennessee United States 37203
30 Vanderbilt - Ingram Cancer Center Nashville Tennessee United States 37232
31 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
32 Texas Oncology - Paris Paris Texas United States 75460
33 NEXT Oncology San Antonio Texas United States 78229
34 Northwest Cancer Specialists Vancouver Washington United States 98684

Sponsors and Collaborators

  • Tizona Therapeutics, Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Tizona Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT04485013
Other Study ID Numbers:
  • TTX-080-001
First Posted:
Jul 24, 2020
Last Update Posted:
Aug 4, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Tizona Therapeutics, Inc
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 4, 2022