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

Tizona Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Cancer

Treatments: Drug: cetuximab; Drug: FOLFIRI; Drug: TTX-080; Drug: pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04485013

TTX-080-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 11 patient groups

Phase 1a, Monotherapy Dose Escalation

Experimental group

Treatment:

Drug: TTX-080

Drug: TTX-080

Drug: TTX-080

Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)

Experimental group

Description:

Arm 1 will enroll subjects with advanced/metastatic, prior checkpoint inhibitor treated Head and Neck Squamous Cell Carcinoma (HNSCC)

Treatment:

Drug: pembrolizumab

Drug: TTX-080

Drug: TTX-080

Drug: TTX-080

Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)

Experimental group

Description:

Arm 2 will enroll subjects with advanced/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Treatment:

Drug: TTX-080

Drug: TTX-080

Drug: cetuximab

Drug: TTX-080

Drug: cetuximab

Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC)

Experimental group

Description:

Arm 3 will enroll subjects with advanced/metastatic colorectal cancer (CRC)

Treatment:

Drug: TTX-080

Drug: TTX-080

Drug: TTX-080

Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapy

Experimental group

Description:

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

Treatment:

Drug: TTX-080

Drug: TTX-080

Drug: cetuximab

Drug: TTX-080

Drug: cetuximab

Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapy

Experimental group

Description:

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

Treatment:

Drug: TTX-080

Drug: TTX-080

Drug: cetuximab

Drug: TTX-080

Drug: cetuximab

Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)

Experimental group

Description:

Arm 6 will enroll subjects with advanced/metastatic non-small cell lung cancer (NSCLC)

Treatment:

Drug: TTX-080

Drug: TTX-080

Drug: TTX-080

Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)

Experimental group

Description:

Arm 7 will enroll subjects with advanced/metastatic prior checkpoint inhibitor treated non-small cell lung cancer (NSCLC)

Treatment:

Drug: pembrolizumab

Drug: TTX-080

Drug: TTX-080

Drug: TTX-080

Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumab

Experimental group

Description:

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

Treatment:

Drug: pembrolizumab

Drug: TTX-080

Drug: TTX-080

Drug: TTX-080

TTX-080 in combination with FOLFIRI plus cetuximab

Experimental group

Description:

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

Treatment:

Drug: TTX-080

Drug: TTX-080

Drug: FOLFIRI

Drug: cetuximab

Drug: TTX-080

Drug: cetuximab

FOLFIRI plus cetuximab

Experimental group

Description:

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

Treatment:

Drug: FOLFIRI

Drug: cetuximab

Drug: cetuximab