TTX-080 +/− Cetuximab/Pembrolizumab for Cancer

Recruiting at 15 trial locations

Overseen By Tizona Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tizona Therapeutics, Inc

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Severe autoimmune, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test a new treatment called TTX-080 (an HLA-G antagonist), either alone or with other cancer drugs like pembrolizumab and cetuximab. The goal is to determine the safety and effectiveness of TTX-080 for people with advanced cancers, including colorectal, lung, breast, and head and neck cancers. Different groups in the trial will test various treatment combinations. This trial may suit those diagnosed with advanced or metastatic cancer who have not found success with other treatments. As a Phase 1 trial, the research focuses on understanding how TTX-080 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on high-dose steroid therapy or other immunosuppressive treatments. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that TTX-080, whether used alone or with other drugs like cetuximab or pembrolizumab, is under study to assess its safety and tolerability. Early results suggest that patients generally tolerate TTX-080 well. Most reported side effects were mild to moderate, such as tiredness, nausea, and some skin reactions, which are common with cancer treatments.

The study is in its early stages, focusing on determining the right dose and identifying any side effects. The drug remains under close observation before advancing to later testing stages. It is important to note that cetuximab and pembrolizumab are already FDA-approved for certain cancers, indicating their safety when used with TTX-080.

For those considering joining this trial, this information provides insight into what researchers have learned about the safety of TTX-080 so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for metastatic colorectal cancer (CRC), which often involve chemotherapy and targeted therapies like cetuximab, TTX-080 stands out by targeting a novel immune pathway. This drug is designed to enhance the body's immune response against cancer cells, potentially offering a new mechanism to combat tumors. Additionally, combining TTX-080 with pembrolizumab or cetuximab might amplify its effectiveness, particularly in patients who have progressed after previous therapies. Researchers are excited because this approach could lead to more personalized and effective treatment options for challenging cancers like CRC, breast cancer, and head and neck cancers.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that TTX-080 blocks a molecule called HLA-G, which helps cancer cells evade the immune system. By blocking HLA-G, the body's natural defenses can fight tumors. In this trial, participants with colorectal cancer (CRC) may receive TTX-080 with cetuximab, a drug that targets cancer cell growth and has shown promising results in improving patient outcomes. For head and neck cancer, some participants will receive TTX-080 with cetuximab, and early trials suggest this combination may help control the disease. Additionally, TTX-080 is being tested with pembrolizumab, a drug that boosts the immune system, for treating various cancers, including aggressive breast cancer and lung cancer, by enhancing the immune response. Overall, early findings suggest TTX-080 could be an effective treatment, but more research is needed to confirm these results. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I'm sorry, I don't understand what you mean by "Abbreviated." Could you please provide more context or information?

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

My cancer is advanced and has spread to other parts.

Exclusion Criteria

History of allergy or hypersensitivity to study treatment components

History of severe autoimmune disease

Subjects with a history of severe hypersensitivity reaction to any monoclonal antibody

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Dose Escalation

Dose escalation to determine the safety, tolerability, MTD or OBD, and the RP2D of TTX-080 as a single agent

8-12 weeks

Phase 1b Dose Expansion

Dose expansion of TTX-080 monotherapy and in combination with pembrolizumab, cetuximab, or FOLFIRI plus cetuximab to evaluate pharmacokinetics, immunogenicity, and anti-tumor activity

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Pembrolizumab
• TTX-080

Trial Overview 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.

How Is the Trial Designed?

Group I: TTX-080 in combination with FOLFIRI plus cetuximab Experimental Treatment 3 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.

Group II: Phase 1b, Dose Expansion: TTX-080 monotherapy (NSCLC) Experimental Treatment 1 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 Treatment 1 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 Treatment 2 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 Treatment 2 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 Treatment 2 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 therapy Experimental Treatment 2 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 therapy Experimental Treatment 2 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 pembrolizumab Experimental Treatment 2 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 Escalation Experimental Treatment 1 Intervention

Group XI: FOLFIRI plus cetuximab Experimental Treatment 2 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.

Who Is Running the Clinical Trial?

Tizona Therapeutics, Inc

Lead Sponsor

Trials

1

Recruited

240+

Published Research Related to This Trial

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

Nivolumab and pembrolizumab are monoclonal antibodies that work by blocking the PD-1 receptor, which helps to enhance the body's immune response against tumors.

Both drugs have been recently approved for treating metastatic melanoma, with nivolumab also approved for non-small cell lung cancer, indicating their efficacy in targeting these specific cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 Blockers. Wolchok, JD.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant efficacy in treating advanced non-small-cell lung cancer (NSCLC) across multiple clinical trials, particularly in patients with PD-L1 expression levels of 1% or higher.

The KEYNOTE studies identified specific patient populations that benefit most from pembrolizumab, highlighting the importance of PD-L1 as a companion diagnostic, while future research will explore its role in earlier stages of cancer treatment and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. Palumbo, G., Carillio, G., Manzo, A., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor known for its antitumor effects, can cause multiple inflammatory adverse events, highlighting the need for awareness of its side effects.

This case emphasizes the importance of early identification of various cutaneous side effects associated with immunotherapy, which can affect patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced sarcoid granulomatous panniculitis and bullous pemphigoid in a single patient. Honigman, AD., Lai, F., Elakis, J., et al.[2021]

In a study of 1959 patients treated with PD-1 or PD-L1 inhibitors, 16.31% experienced new-onset cardiac complications, with heart failure being the most common issue (12.57%).

Patients receiving PD-L1 inhibitors had a significantly lower risk of cardiac complications and all-cause mortality compared to those treated with PD-1 inhibitors, indicating that PD-L1 inhibitors may be a safer option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Cardiovascular Complications following prescription of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors: a propensity-score matched Cohort Study with competing risk analysis. Zhou, J., Lee, S., Lakhani, I., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

In a review of 567 reports of immune-mediated necrotizing myopathy (IMNM), 14 cases were associated with pembrolizumab, indicating a significant link between this treatment and the adverse event, with a reporting odds ratio of 17.59.

The study emphasizes the importance of updated diagnostic criteria for IMNM and suggests that better collaboration between oncologists and neurologists is needed to address these neurological complications related to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-mediated necrotizing myopathy with pembrolizumab: a specific neuromuscular entity. Trenque, T., Lepoix, E., Trenque, A., et al.[2022]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, is generally well tolerated, but can lead to rare immune-mediated adverse effects such as pleuropericarditis, as seen in a case involving a 64-year-old female patient.

The patient was effectively treated with colchicine, furosemide, and methylprednisolone, leading to symptom improvement and a decision to discontinue pembrolizumab, after which she remained asymptomatic for six months, highlighting the importance of recognizing and managing potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. Suarez, ZK., Finke, AC., Hospedales, E., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2524

Results from phase 1a/1b analyses of TTX-080, a first in ... This Ph1a/1b study evaluated the safety and preliminary efficacy of TTX-080 alone or in combination with cetuximab (Cetx) or pembrolizumab (Pem) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04485013

Study Details | NCT04485013 | TTX-080 HLA-G Antagonist ... 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 ...

3. tizonatx.com tizonatx.com/file.cfm/87/docs/tizona_ttx-080_poster_final.pdf

Table 2. Response Rates by Central Review of TTX-080 + Herein, we report safety and efficacy of TTX-080 + cetuximab primarily from Anti-EGFR naïve ... HLA-G Antagonist, in Combination with Cetuximab in ...

4. tizonatx.com tizonatx.com/news/press-releases/051524/

Phase 1b TTX-080 clinical data “These Phase 1b clinical results boost our confidence that TTX-080 in combination with cetuximab may improve clinical outcomes in patients with biomarker- ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT445264

Results from phase 1a/1b analyses of TTX-080, a first in ... ASCO Overview · Press Center · Careers at ASCO · Mobile Apps · Conference Center Rental · Association for Clinical Oncology.

6. ctv.veeva.com ctv.veeva.com/study/ttx-080-hla-g-antagonist-in-subjects-with-advanced-cancers

TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers TTX-080-001 is a Phase 1, open label, dose escalation and dose expansion clinical study to determine the safety, tolerability, ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04485013/

Clinical Trial: NCT04485013 - Solid Tumor This first-in-human (FIH) study has been designed to evaluate the safety, tolerability, and preliminary antitumor activity of TTX-080 as ...