What side effects are associated with this type of intervention?

Common treatments for Squamous Cell Carcinoma (SCC), especially those involving immunotherapy and targeted therapies like autologous T cells engineered with the Sleeping Beauty transposon/transposase system, often result in side effects such as dermatological toxicities (rash, pruritus), gastrointestinal issues (diarrhea, colitis), and systemic effects (fatigue, fever). Immune-related adverse events (irAEs) can also occur, potentially impacting the liver, lungs, and endocrine glands.

What prior FDA approvals exist?

FDA-approved treatments for Squamous Cell Carcinoma (SCC) have included various immunotherapies and targeted therapies. Notably, immune checkpoint inhibitors such as pembrolizumab (Keytruda) and nivolumab (Opdivo) have been approved for treating recurrent or metastatic SCC. These drugs work by targeting PD-1, a protein on T cells that helps keep the body's immune responses in check. While these treatments are not identical to the autologous T cells engineered with the Sleeping Beauty transposon/transposase system, they share a common goal of enhancing the immune system's ability to fight cancer. Other targeted therapies for SCC include cetuximab (Erbitux), which targets the epidermal growth factor receptor (EGFR).

What other types of research exist?

Promising novel alternatives for Squamous Cell Carcinoma patients include: 1) 5-aminolevulinic acid-based photodynamic therapy, which has shown efficacy in treating condylomata acuminata and may be applicable to SCC. 2) Beremagene geperpavec (B-VEC), a gene therapy using a modified herpes simplex virus to deliver functional genes to skin cells, which has shown promise in treating epidermolysis bullosa and could be adapted for SCC. 3) PD-1 blockade therapies, such as nivolumab, which have demonstrated activity in other cancers and may offer benefits for SCC patients.

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CAR T-cell Therapy

Engineered T-Cell Therapy for Cancer

Phase 1 & 2

Waitlist Available

Led By Scott Kopetz, MD, PhD

Research Sponsored by Ziopharm

Eligibility Criteria Checklist

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

Must have

Patients must have evaluable or measurable disease per RECIST 1.1 with at least one lesion that can be measured that is not the biopsied lesion

Patients who have completed the HLA Typing and Tumor Neoantigen Identification Protocol (TCR001-002) and for whom a TCR(s) matching the subject's somatic mutation(s) and HLA type restriction combination is available in Alaunos' Clinical TCR library

Must not have

Active unstable or clinically significant medical condition

Severe chronic respiratory condition

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests a new treatment where a patient's own immune cells are modified to better fight cancer. It targets patients with certain solid tumors that haven't responded to other treatments. The modified cells are designed to recognize and attack cancer cells more effectively. This new approach extends the capacity of the patient's own immune cells to detect and eliminate cancer cells.

Who is the study for?

Adults with certain solid tumors like lung, ovarian, colorectal, pancreatic cancer who've tried at least one treatment without success. They must be in fairly good health otherwise (ECOG 0 or 1), have a tumor that can be measured and not currently pregnant or breastfeeding. Excluded are those with bleeding disorders, compromised immune systems, severe mental illness affecting study compliance, active brain metastases, recent major heart issues or other serious medical conditions.

What is being tested?

The trial is testing T cells modified to target specific cancer cell markers using Sleeping Beauty transposon/transposase system alongside Aldesleukin (IL-2). It's for patients whose cancers haven't responded to standard treatments and involves multiple phases to assess safety and effectiveness.

What are the potential side effects?

Possible side effects include reactions related to the immune system attacking normal cells leading to inflammation in various organs. There might also be typical symptoms associated with immunotherapies such as fatigue, feverish feelings or chills due to the activation of the immune system.

Eligibility Criteria

Inclusion Criteria

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

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I have a cancer lesion that can be measured, separate from the one biopsied.

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I have completed specific genetic tests and there is a matching treatment in the clinical library.

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I am 18 years old or older.

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My condition is pancreatic cancer.

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I am not pregnant or breastfeeding.

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I have ovarian cancer.

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I have endometrial cancer.

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 unstable or significant health conditions.

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I have a severe long-term lung problem.

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I am currently taking steroid medication.

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I do not have any active, uncontrolled infections.

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I have a major blockage or bleeding in my airways that can't be relieved.

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I have a history of bleeding disorders or unexplained severe bleeding.

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I have active cancer spread to my brain.

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I have or had another type of cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Phase I: To define the incidence of dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of T-Cell Receptor T cells

Phase II: Incidence of Adverse Events as characterized by type, frequency, severity (NCI CTCAE Version 5.0), timing, seriousness, and relationship to study therapy.

Phase II: Objective response rate (ORR) evaluated by Investigator assessments using Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Secondary study objectives

Phase I: To evaluate the feasibility of neoantigen-specific T-Cell Receptor T cells (herein referred to as TCR-T cells) manufacturing.

Phase I: To investigate translational hypotheses related to TCR-T cell persistence without IL-2 (Arm A) or with IL-2 (Arm B).

Phase II: To confirm Phase I results of translational hypotheses related to TCR-T cell persistence without IL-2 (Arm A) or with IL-2 (Arm B).

Other study objectives

Phase I: To evaluate the objective response rate (ORR) (RECIST and iRECIST criteria) of subjects with solid cancers who receive TCR-T cell drug product.

Phase I: To explore translational hypotheses related to molecular signatures, mechanism of action, immunogenicity, and serum cytokine profiles associated with TCR-T cell drug product infusion without IL-2 (Arm A) or with IL-2 (Arm B).

Phase II: To evaluate anti-tumor activity (ORR) (iRECIST) of TCR-T cell drug product without IL-2 (Arm A) or with IL-2 (Arm B) in each of the tumor types.

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Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: TCR-T Cell Drug Product with Aldesleukin (IL-2)Experimental Treatment2 Interventions

Phase I: Dose-escalation of TCR-T Cell Drug Product with Aldesleukin (IL-2) Phase II: Single dose of TCR-T Cell Drug Product with Aldesleukin (IL-2) after MTD/RP2D determine in Phase I portion of the study

Group II: TCR-T Cell Drug ProductExperimental Treatment1 Intervention

Phase I: Dose-escalation of TCR-T Cell Drug Product Phase II: Single dose of TCR-T Cell Drug Product after MTD/RP2D determine in Phase I portion of the study

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Aldesleukin

FDA approved

0 / 15Eligibility 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

The most common treatments for Squamous Cell Carcinoma (SCC) include surgical resection, radiation therapy, and chemotherapy. These treatments work by physically removing the tumor, damaging the DNA of cancer cells to prevent their replication, and using drugs to kill rapidly dividing cells, respectively. Recently, immunotherapy has emerged as a promising approach, particularly for advanced cases. Autologous T cells engineered with the Sleeping Beauty transposon/transposase system to express T-cell receptors (TCRs) reactive against neoantigens represent a novel treatment strategy. This method involves modifying a patient's own T cells to better recognize and attack cancer cells, enhancing the body's immune response against the tumor. This is particularly important for SCC patients as it offers a targeted approach that can potentially improve outcomes and reduce side effects compared to traditional therapies.

The Novel Therapeutic Landscape for Relapsed/Refractory Diffuse Large B Cell Lymphoma.Human Papillomavirus Induced Cervical and Oropharyngeal Cancers: From Mechanisms to Potential Immuno-therapeutic Strategies.The forgotten woman's cancer: vulvar squamous cell carcinoma (VSCC) and a targeted approach to therapy.