What is the mechanism of action of this treatment?

The most common treatments for Head and Neck Squamous Cell Carcinoma (HNSCC) include surgery, radiation therapy, chemotherapy, and immunotherapy. Surgery involves physically removing the tumor, which is crucial for localized disease. Radiation therapy uses high-energy rays to kill cancer cells by damaging their DNA, making it effective for both primary and adjuvant treatment. Chemotherapy employs cytotoxic drugs to target rapidly dividing cells, often used in combination with radiation for advanced stages. Immunotherapy, such as immune checkpoint inhibitors, enhances the body's immune response against cancer cells. The investigational therapy NT-175, which uses genetically engineered T cells to target the TP53 R175H mutation, represents a novel approach by specifically directing the immune system to attack cancer cells with this mutation. This targeted mechanism is particularly important for HNSCC patients with specific genetic profiles, offering a more personalized and potentially effective treatment option.

What side effects are associated with this type of intervention?

Common treatments for Head and Neck Squamous Cell Carcinoma (HNSCC) include radiation therapy (RT), chemoradiation, and systemic therapies. Known side effects of these treatments can include mucositis, which is inflammation and ulceration of the mucous membranes, and may require tube feeding in severe cases. Higher doses of RT are associated with increased rates of late grade 3 and 4 toxicities such as ulceration, soft tissue necrosis, fibrosis, dysphagia, and fistula/osteonecrosis. Systemic therapies, including those involving genetically engineered T cells like NT-175, may also cause severe skin reactions, hypomagnesemia, and infusion-related reactions. These side effects highlight the importance of careful management and monitoring during treatment.

What prior FDA approvals exist?

Prior FDA approvals for the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC) include cetuximab, an EGFR-targeting monoclonal antibody, approved for use with radiation therapy and as a single agent in metastatic cases. Additionally, PD-1 inhibitors such as nivolumab and pembrolizumab have been approved for patients with metastatic or recurrent HNSCC who have previously undergone platinum-based chemotherapy. These treatments highlight advancements in targeted and immunotherapy approaches, although they do not involve genetically engineered T cells like NT-175.

What other types of research exist?

Promising novel alternatives to NT-175 for HNSCC patients include Evofosfamide, a hypoxia-activated prodrug showing preclinical efficacy in HPV-negative HNSCC, and Rigosertib, which has demonstrated effectiveness in direct patient tumor xenografts of HNSCC, particularly those with PI3KCA and TP53 mutations.

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CAR T-cell Therapy

Engineered T-Cell Therapy for Cancer

Phase 1

Recruiting

Research Sponsored by Neogene Therapeutics, Inc.

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 days after infusion

Awards & highlights

No Placebo-Only Group

Summary

This trial tests NT-175, a personalized treatment made from a patient's own immune cells, in patients with advanced cancers that have a specific genetic mutation. The treatment works by enhancing the immune system to attack cancer cells.

Who is the study for?

Adults over 18 with advanced solid tumors positive for HLA-A*02:01 and TP53 R175H mutation, who've tried standard treatments without cure. Eligible cancers include NSCLC, colorectal adenocarcinoma, head and neck squamous cell carcinoma, pancreatic adenocarcinoma, breast cancer or other solid tumors. Must have measurable disease and be in good physical condition.

What is being tested?

The trial is testing NT-175 T cells engineered to target the TP53 R175H mutation in various advanced solid tumors. It's a Phase I study assessing safety and how well these modified T cells work against the cancer.

What are the potential side effects?

Potential side effects are not specified but may include immune reactions due to engineered T cells targeting cancer mutations, as well as typical risks associated with immunotherapies such as inflammation or tissue damage at tumor sites.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 days after infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 days after infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 days after infusion for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 1: Safety of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors

Part 2: Further Evaluate the safety of NT-175 at the RP2D in subjects with unresectable, advanced, and/or metastatic solid tumors

Part 2: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors

Secondary study objectives

Part 1: Preliminary anti-tumor activity of NT-175 in subjects with unresectable, advanced, and/or metastatic solid tumors

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Part 2: Disease Cohort ExpansionExperimental Treatment1 Intervention

TCR T Cell Product at the RP2D

Group II: Part 1: Disease Histology EvaluationExperimental Treatment1 Intervention

TCR T Cell Product at the MTD

Group III: Dose Escalation and ExpansionExperimental Treatment1 Intervention

Dose Escalation of TCR T cell product

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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

The most common treatments for Head and Neck Squamous Cell Carcinoma (HNSCC) include surgery, radiation therapy, chemotherapy, and immunotherapy. Surgery involves physically removing the tumor, which is crucial for localized disease. Radiation therapy uses high-energy rays to kill cancer cells by damaging their DNA, making it effective for both primary and adjuvant treatment. Chemotherapy employs cytotoxic drugs to target rapidly dividing cells, often used in combination with radiation for advanced stages. Immunotherapy, such as immune checkpoint inhibitors, enhances the body's immune response against cancer cells. The investigational therapy NT-175, which uses genetically engineered T cells to target the TP53 R175H mutation, represents a novel approach by specifically directing the immune system to attack cancer cells with this mutation. This targeted mechanism is particularly important for HNSCC patients with specific genetic profiles, offering a more personalized and potentially effective treatment option.