What side effects are associated with this type of intervention?

Common side effects of cancer treatments similar to the HLA-G inhibitor TTX-080, such as immune checkpoint inhibitors (e.g., pembrolizumab) and EGFR inhibitors (e.g., cetuximab), include immune-related adverse events (irAEs) like pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions (rash, pruritus). These treatments can also cause fatigue, fever, and gastrointestinal issues such as diarrhea. Severe side effects may require immunosuppressive treatments like steroids. Monitoring and managing these side effects are crucial for patient safety and treatment efficacy.

What prior FDA approvals exist?

The FDA has approved several immunotherapy drugs for the treatment of cancer. Notable examples include pembrolizumab (Keytruda) and nivolumab (Opdivo), both of which are PD-1 inhibitors used to treat various cancers such as melanoma, non-small cell lung cancer, and head and neck cancer. Additionally, ipilimumab (Yervoy), a CTLA-4 inhibitor, has been approved for melanoma. These drugs work by enhancing the body's immune response against cancer cells. While HLA-G inhibitors like TTX-080 are still under investigation, they represent a promising new approach in the field of cancer immunotherapy.

What other types of research exist?

Promising novel alternatives to TTX-080 for cancer patients include: 1) Pembrolizumab plus cetuximab, which is being investigated for treatment-refractory metastatic head and neck cancer. 2) GVAX, Lucanix, and L-BLP25, which are vaccine approaches for non-small cell lung cancer. 3) Anti-PD-1 or PD-L1 therapies, such as nivolumab, which have shown promise in various cancers including large cell neuroendocrine carcinoma of the lung. 4) Sipuleucel-T and ipilimumab, which are being developed for castrate-resistant prostate cancer.

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HLA-G Inhibitor

TTX-080 +/− Cetuximab/Pembrolizumab for Cancer

Phase 1

Recruiting

Research Sponsored by Tizona Therapeutics, Inc

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 AND life expectancy of at least 12 weeks

Subject with histological diagnosis of advanced/metastatic cancer

Must not have

Uncontrolled intercurrent illness or other active malignancy requiring ongoing treatment

Receiving high-dose systemic steroid therapy or any other form of immunosuppressive therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests TTX-080, a new drug, alone and with other cancer drugs in patients with hard-to-treat cancers. It works by helping the immune system find and attack cancer cells.

Who is the study for?

This trial is for adults with advanced or metastatic cancer who are in fairly good health (able to perform daily activities without significant assistance) and have a life expectancy of at least 12 weeks. They must be able to consent to the study, not have severe allergies to treatment components, no recent use of other investigational drugs, no high-dose steroids or immunosuppressants, and no uncontrolled illnesses.

What is being tested?

The TTX-080 clinical trial is testing the safety and optimal dosing of a new drug called TTX-080 alone or combined with pembrolizumab or cetuximab in patients with resistant cancers. It's an early-phase study where researchers gradually increase doses to find what's safe and potentially effective.

What are the potential side effects?

Possible side effects include allergic reactions related to the treatments' components, immune system-related issues due to HLA-G inhibition by TTX-080, infusion reactions from monoclonal antibodies like pembrolizumab/cetuximab, fatigue, skin reactions from EGFR inhibition by cetuximab.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am mostly active and my doctor expects me to live at least 12 more weeks.

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My cancer is advanced and has spread to other parts.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any other active cancers or serious illnesses that are not under control.

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I am currently on high-dose steroids or other drugs that weaken my immune system.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

11Treatment groups

Experimental Treatment

Group I: TTX-080 in combination with FOLFIRI plus cetuximabExperimental Treatment3 Interventions

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

Group II: Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC)Experimental Treatment1 Intervention

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

Group III: Phase 1b, Dose Expansion: TTX-080 monotherapy (CRC)Experimental Treatment1 Intervention

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

Group IV: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (NSCLC)Experimental Treatment2 Interventions

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

Group V: Phase 1b, Dose Expansion: TTX-080 in combination with pembrolizumab (HNSCC)Experimental Treatment2 Interventions

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

Group VI: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (HNSCC)Experimental Treatment2 Interventions

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

Group VII: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), prior anti-EGFR therapyExperimental Treatment2 Interventions

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

Group VIII: Phase 1b, Dose Expansion: TTX-080 in combination with cetuximab (CRC), no prior anti-EGFR therapyExperimental Treatment2 Interventions

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

Group IX: Phase 1b, Dose Expansion: TTX-080 as monotherapy OR in combination with pembrolizumabExperimental Treatment2 Interventions

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

Group X: Phase 1a, Monotherapy Dose EscalationExperimental Treatment1 Intervention

Group XI: FOLFIRI plus cetuximabExperimental Treatment2 Interventions

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

First Studied

Drug Approval Stage

How many patients have taken this drug

FOLFIRI

2005

Completed Phase 3

~5860

cetuximab

2000

Completed Phase 3

~7290

pembrolizumab

2017

Completed Phase 3

~5890

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immunotherapies, such as checkpoint inhibitors (PD-1 and PD-L1 inhibitors) and CAR T-cell therapies, enhance the immune system's ability to recognize and destroy cancer cells. Checkpoint inhibitors prevent cancer cells from evading immune detection, while CAR T-cell therapies engineer T-cells to target specific cancer antigens. These targeted approaches are significant for cancer patients as they can provide more effective and personalized treatment options with potentially fewer side effects compared to traditional therapies like chemotherapy.

Advances in Immunotherapies for Gliomas.