Cancer
Conditions
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
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.
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. Only arm 9 and 10 are currently open to enrollment.
Interventions
DRUGTTX-080
Variable dose (Q3W)
DRUGpembrolizumab
Specified dose (Q3W)
DRUGcetuximab
Specified dose on specified days
DRUGFOLFIRI
Specified dose (Q2W)
Sponsors
Tizona Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Abbreviated Inclusion Criteria: 1. Subject with histological diagnosis of advanced/metastatic cancer \[currently enrolling in CRC only\] 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
Design outcomes
Primary
| 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
| 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 |
Countries
United States
Outcome results
None listed