TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers
Status
RECRUITING
Phase
PHASE1
Age
≥ 18 Years
Enrollments
240Conditions
CancerDrugs
TTX-080, TTX-080, pembrolizumab, cetuximab, FOLFIRI, cetuximab, TTX-080Summary
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.
Locations
18 locations Found with status Recruiting
Status
- RECRUITING
Contact Person
- 520-886-0206
Status
- RECRUITING
Contact Person
- 303-388-4876
Status
- RECRUITING
Contact Person
- 203-737-5342
Status
- RECRUITING
Contact Person
- 386-231-4060
Status
- RECRUITING
Contact Person
- 904-269-6526
Status
- RECRUITING
Contact Person
- 352-547-1958
Status
- RECRUITING
Contact Person
- 301-933-3216
Status
- RECRUITING
Contact Person
- 617-582-8705
Status
- RECRUITING
Contact Person
- 651-254-3602
Status
- RECRUITING
Contact Person
- 402-691-6971
Status
- RECRUITING
Contact Person
- 732-235-3253
Status
- RECRUITING
Contact Person
- 513-584-5680
Status
- RECRUITING
Contact Person
- 405-271-8001
Status
- RECRUITING
Contact Person
- 412-647-8587
Status
- RECRUITING
Contact Person
- 615-524-4203
Status
- RECRUITING
Contact Person
- 214-370-1000
Status
- RECRUITING
Contact Person
- 903-785-0031
Status
- RECRUITING
Contact Person
- 703-280-5290
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
Study Plan
Phase 1a, Monotherapy Dose Escalation
DRUG:
TTX-080Description:
Variable dose (Q3W)
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)
DRUG:
TTX-080Description:
Specified dose (Q3W)DRUG:
pembrolizumabDescription:
Specified dose (Q3W)
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)
DRUG:
TTX-080Description:
Specified dose (Q3W)DRUG:
cetuximabDescription:
Specified dose on specified days
Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC)
EXPERIMENTAL
Arm 3 will enroll subjects with advanced/metastatic colorectal cancer (CRC)
DRUG:
TTX-080Description:
Specified dose (Q3W)
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
DRUG:
TTX-080Description:
Specified dose (Q3W)DRUG:
cetuximabDescription:
Specified dose on specified days
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
DRUG:
TTX-080Description:
Specified dose (Q3W)DRUG:
cetuximabDescription:
Specified dose on specified days
Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)
EXPERIMENTAL
Arm 6 will enroll subjects with advanced/metastatic non-small cell lung cancer (NSCLC)
DRUG:
TTX-080Description:
Specified dose (Q3W)
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)
DRUG:
TTX-080Description:
Specified dose (Q3W)DRUG:
pembrolizumabDescription:
Specified dose (Q3W)
Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab
EXPERIMENTAL
Arm 8: TTX-080 monotherapy:nn* Advanced/metastatic, prior checkpoint inhibitor treated renal cell carcinoma with predominance of clear cell componentn* Advanced/metastatic acral melanomannArm 8: TTX-080 in combination with pembrolizumab:nnu2022 Advanced/metastatic triple-negative breast cancer (estrogen and progesterone receptor negative and HER2 negative) who has received a prior checkpoint inhibitor
DRUG:
TTX-080Description:
Specified dose (Q3W)DRUG:
pembrolizumabDescription:
Specified dose (Q3W)
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 or irinotecan containing regimen
DRUG:
FOLFIRIDescription:
Specified dose (Q2W)DRUG:
cetuximabDescription:
Specified dose (Q2W)DRUG:
TTX-080Description:
Specified dose (Q2W)
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 or irinotecan containing regimen
DRUG:
FOLFIRIDescription:
Specified dose (Q2W)DRUG:
cetuximabDescription:
Specified dose (Q2W)
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
Secondary Outcome Measures
Duration of Response, Progression Free Survival per RECIST 1.1
Overall Survival
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
Tolerability: The number of cycles of TTX-080 received by patients before discontinuing due to unmanageable drug reactions
Serum levels of Anti Drug Antibody against TTX-080
Cmax: Maximum Observed Plasma Concentration for TTX-080
Tmax: Time to Reach the Cmax for TTX-080
AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for TTX-080
AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for TTX-080
Timeline
Last Updated
November 5, 2024Start Date
July 24, 2020Today
February 5, 2025Completion Date ( Estimated )
June 1, 2027
Sponsors of this trial
Lead Sponsor
Tizona Therapeutics, Inc
RECRUITING 
21 - 64 Years