Customized TCR-T Cell Therapy for Cancer

Not currently recruiting at 20 trial locations

Overseen By Erica Gagnon

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TScan Therapeutics, Inc.

Must not be taking: Antiarrhythmics, Corticosteroids, Antimicrobials, others

Disqualifiers: Cardiac disease, Stroke, CNS metastases, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with certain advanced cancers, such as lung or cervical cancer, who have no other curative options. The study tests different combinations of engineered T cells (a type of immune cell) to determine if they can safely and effectively target and fight cancer cells. This includes TCR-T cell therapy, such as TSC-200-A0201 and TSC-204-A0201, designed to target specific proteins on cancer cells. It is intended for individuals whose tumors express certain proteins and have specific genetic markers (HLA types). Participants should have solid tumors that cannot be surgically removed and have not responded to standard treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic corticosteroid therapy greater than 10 mg of prednisone daily within 7 days of enrollment, and you cannot receive another anti-cancer therapy concurrently.

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

Research has shown that the TCR-T cell therapies in this trial, such as TSC-200-A0201 and TSC-204-A0201, are in the early stages of safety testing. These therapies are being tried in humans for the first time. The main goal is to assess their safety and how well people tolerate them. So far, the FDA has not approved these treatments for any condition, and detailed safety information from human trials is not yet available.

Since these treatments are in their initial human tests, information on safety is limited. Early studies focus on identifying any serious side effects. Because they are in the first phase of testing, there might not be enough data yet to fully understand all potential risks. However, the FDA has allowed these treatments to begin testing, indicating that earlier research demonstrated some level of safety.

Participants in these trials may experience side effects, which is common in early trials. It is important for participants to discuss potential risks with their doctors before joining. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the customized TCR-T cell therapies because they offer a personalized approach to treating cancer. Unlike traditional treatments such as chemotherapy or radiation that target rapidly dividing cells, TCR-T therapies are engineered to recognize and attack specific cancer cells based on their unique antigens. This precision targeting aims to enhance efficacy and minimize damage to healthy cells. Additionally, these therapies leverage the body's immune system, potentially leading to more durable responses and fewer side effects compared to conventional treatments. With these innovations, TCR-T cell therapy represents a promising advancement in the fight against cancer.

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

Research shows that TScan Therapeutics is developing a personalized TCR-T cell therapy to treat various solid tumors. In this trial, participants may receive different treatment combinations. One treatment, TSC-200-A0201, targets HPV16-positive cancers, which are linked to many cervical cancers, by recognizing specific cancer markers. TSC-204-A0201 and TSC-204-C0702 focus on melanoma by identifying certain proteins in tumors, showing promise in early lab tests. TSC-203-A0201 and TSC-201-B0702 aim to target unique tumor markers, potentially offering personalized treatment options. Early data suggest these treatments may effectively target cancer cells by recognizing specific markers often found in tumors, offering hope for treating cancers that have been difficult to manage with other therapies. ^{3 6 7 8 9}

Who Is on the Research Team?

Dawn Pinchasik, MD

Principal Investigator

TScan Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that can't be surgically removed or have spread, and who've tried all other treatments without success. They must match specific genetic markers (HLA types) and their cancer should express certain proteins (MAGE-A1/HPV16-E7). Good physical condition is required, they must understand the study, and not be on high-dose steroids or have serious heart issues.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer is advanced, cannot be surgically removed, and has not responded to standard treatments.

At least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Exclusion Criteria

I have not taken more than 10 mg of prednisone daily in the last week.

I have not had a stroke or TIA in the last year.

I regularly need extra oxygen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Participants undergo leukapheresis to collect cells for TCR-T product manufacturing

1 week

1 visit (in-person)

Lymphodepletion and Treatment

Participants undergo lymphodepletion and receive one or two doses of TCR-T cell therapy

4-6 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• TSC-200-A0201
• TSC-204-A0201
• TSC-204-A0201 + TSC-200-A0201
• TSC-204-A0201 + TSC-204-C0702
• TSC-204-C0702

Trial Overview

The study tests personalized T cell therapies where patients' own immune cells are engineered to target cancer. It's an open-label trial meaning everyone knows what treatment they're getting. Participants will receive one of several therapy combinations after chemotherapy intended to prepare their body for the new cells.

How Is the Trial Designed?

Group I: T-Plex Combination Cohort F + G Experimental Treatment 1 Intervention

TSC-201-B0702 + TSC-202-A0201

Group II: T-Plex Combination Cohort E + G Experimental Treatment 1 Intervention

TSC-204-A0101 + TSC-202-A0201

Group III: T-Plex Combination Cohort E + F Experimental Treatment 2 Interventions

TSC-204-A0101 + TSC-201-B0702

Group IV: T-Plex Combination Cohort D + G Experimental Treatment 1 Intervention

TSC-203-A0201 + TSC-202-A0201

Group V: T-Plex Combination Cohort D + F Experimental Treatment 1 Intervention

TSC-203-A0201 + TSC-201B0702

Group VI: T-Plex Combination Cohort D + E Experimental Treatment 1 Intervention

TSC-203-A0201 + TSC-204A0101

Group VII: T-Plex Combination Cohort C+ G Experimental Treatment 1 Intervention

TSC-200-A0201 + TSC-202-A0201

Group VIII: T-Plex Combination Cohort C + F Experimental Treatment 1 Intervention

TSC-200-A0201 + TSC-201B0702

Group IX: T-Plex Combination Cohort C + E Experimental Treatment 1 Intervention

TSC-200-A0201 + TSC-204-A0101

Group X: T-Plex Combination Cohort C + D Experimental Treatment 1 Intervention

TSC-200-A0201 + TSC-203-A0201

Group XI: T-Plex Combination Cohort B + G Experimental Treatment 1 Intervention

TSC-204-C0702 + TSC-202-A0201

Group XII: T-Plex Combination Cohort B + F Experimental Treatment 1 Intervention

TSC-204-C0702 + TSC-201B0702

Group XIII: T-Plex Combination Cohort B + E Experimental Treatment 1 Intervention

TSC-204-C0702 + TSC-204-A0101

Group XIV: T-Plex Combination Cohort B + D Experimental Treatment 1 Intervention

TSC-204-C0702 + TSC-203-A0201

Group XV: T-Plex Combination Cohort B + C Experimental Treatment 1 Intervention

TSC-204-C0702 and TSC-200-A0201

Group XVI: T-Plex Combination Cohort A + G Experimental Treatment 1 Intervention

TSC-204-A0201 + TSC-202-A0201

Group XVII: T-Plex Combination Cohort A + F Experimental Treatment 1 Intervention

TSC-204-A0201 + TSC-201-B0702

Group XVIII: T-Plex Combination Cohort A + E Experimental Treatment 1 Intervention

TSC-204-A0201 + TSC-204-A0101

Group XIX: T-Plex Combination Cohort A + D Experimental Treatment 1 Intervention

TSC-204-A0201 + TSC-203-A0201

Group XX: T-Plex Combination Cohort A + C Experimental Treatment 2 Interventions

TSC-204-A0201 and TSC-200-A0201

Group XXI: T-Plex Combination Cohort A + B Experimental Treatment 1 Intervention

TSC-204-A0201 and TSC-204-C0702

Group XXII: Monotherapy Cohort G Experimental Treatment 1 Intervention

TSC-202-A0201

Group XXIII: Monotherapy Cohort F Experimental Treatment 1 Intervention

TSC-201-B0702

Group XXIV: Monotherapy Cohort E Experimental Treatment 1 Intervention

TSC-204-A0101

Group XXV: Monotherapy Cohort D Experimental Treatment 2 Interventions

TSC-203-A0201

Group XXVI: Monotherapy Cohort C Experimental Treatment 1 Intervention

TSC-200-A0201

Group XXVII: Monotherapy Cohort B Experimental Treatment 1 Intervention

TSC-204-C0702

Group XXVIII: Monotherapy Cohort A Experimental Treatment 1 Intervention

TSC-204-A0201

Who Is Running the Clinical Trial?

TScan Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

1,400+

Published Research Related to This Trial

A new method was developed to create a library of T-cell receptors (TCRs) from frozen tumor biopsies, allowing for the rapid identification of TCR genes that target various tumor antigens, which is crucial for personalized cancer therapies.

When tested, T cells engineered with these tumor-specific TCRs showed strong antitumor effects in a tumor xenograft model, demonstrating the potential of this approach for effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Construction of Antitumor T-cell Receptor Vectors from Frozen Tumors for Engineered T-cell Therapy. Tsuji, T., Yoneda, A., Matsuzaki, J., et al.[2019]

The study analyzed T cell receptor (TCR) diversity in blood and tumor samples from 9 patients with advanced colorectal cancer (CRC) treated with a combination of peptide vaccines and chemotherapy, revealing that TCR populations in tumors differ significantly from those in blood.

A decrease in TCR diversity in tumor tissues during treatment was associated with longer progression-free survival in some patients, suggesting that TCR diversity could serve as a predictive biomarker for the effectiveness of immunochemotherapy in advanced CRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer. Tamura, K., Hazama, S., Yamaguchi, R., et al.[2020]

T cell receptors (TCRs) are being developed as a promising class of cancer therapies that can specifically target proteins expressed by cancer cells, including neoantigens and viral oncoproteins, enhancing the immune response against tumors.

Current clinical data show that TCR-based therapies, such as adoptive cell transfer and TCR bispecific engagers, have demonstrated significant antitumor potential across various human cancers, although challenges like HLA restriction and cross-reactivity remain in their development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cell receptor therapeutics: immunological targeting of the intracellular cancer proteome. Klebanoff, CA., Chandran, SS., Baker, BM., et al.[2023]

Engineered T cell therapies, like CAR T cells and TCR T cell therapies, have shown remarkable efficacy in treating certain blood cancers, highlighting their potential as a powerful tool in cancer immunotherapy.

However, these therapies also pose unique safety challenges, such as cytokine release syndrome and neurotoxicity, which require careful nonclinical safety assessments to ensure patient safety during development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. Lebrec, H., Maier, CC., Maki, K., et al.[2022]

A new T cell receptor mimic (TCRm) therapy targeting alpha-fetoprotein in hepatocellular carcinoma (HCC) demonstrated potent activity against cancer cells while showing no significant adverse effects in a safety assessment, indicating a promising safety profile.

In a clinical case, one patient with metastatic HCC achieved complete remission after nine months of treatment, highlighting the potential efficacy of this TCRm-based therapy in treating a cancer with limited existing options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation and promise of a TCR mimic antibody for cancer immunotherapy of hepatocellular carcinoma. Liu, C., Liu, H., Dasgupta, M., et al.[2022]

The study developed a novel immunotherapy using genetically engineered T cells that express a specific T-cell receptor (TCR) targeting melanoma-associated antigen (MAGE)-A4, which showed enhanced antitumor activity in both mice and a patient with uterine leiomyosarcoma.

By using small interfering RNA to downregulate the endogenous TCR, the modified T cells demonstrated improved surface expression of the tumor-specific TCR and increased effectiveness in killing tumor cells, suggesting a promising approach for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell receptor gene therapy targeting melanoma-associated antigen-A4 by silencing of endogenous TCR inhibits tumor growth in mice and human. Sun, Q., Zhang, X., Wang, L., et al.[2021]

This study successfully used CRISPR-Cas9 technology to create personalized T cells that can target specific cancer mutations by knocking out the patients' own T cell receptors and inserting new, neoantigen-specific T cell receptors (neoTCRs).

In a phase I clinical trial involving 16 patients with refractory solid cancers, the engineered T cells showed the ability to persist in the body and traffic to tumors, although most patients experienced disease progression, highlighting the need for further research on efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-viral precision T cell receptor replacement for personalized cell therapy. Foy, SP., Jacoby, K., Bota, DA., et al.[2023]

The study developed an affinity-enhanced T cell receptor (TCR) targeting the MAGE A3 antigen for cancer therapy, which showed promising preclinical results with no off-target effects; however, it led to a serious adverse event in patients, indicating potential safety risks.

Post-adverse event investigations revealed that the TCR also recognized a peptide from the muscle protein Titin, suggesting that off-target recognition can occur in vivo, emphasizing the need for improved preclinical testing methods to prevent such toxicities in future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Cameron, BJ., Gerry, AB., Dukes, J., et al.[2023]

A new synthetic T-cell receptor (TCR) targeting PD-L1 has been developed to enhance CAR-T therapy's effectiveness against solid tumors, addressing the issue of T-cell exhaustion caused by inhibitory molecules in the tumor environment.

In laboratory tests, the engineered TCRs demonstrated the ability to activate T cells and kill tumor cells, with the γ-TCRγδ variant showing superior effectiveness in an in vivo xenograft model compared to the δ-TCRγδ variant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-based binding domain fused to TCRγ chain facilitates T cell cytotoxicity for potent anti-tumor response. Chen, Z., Lin, C., Pei, H., et al.[2023]

Personalized TCR-T cell therapy, which uses T-cell receptors from tumor-specific T cells, shows significant therapeutic effects against patient-derived tumors, indicating its potential as an effective immunotherapy.

The presence of tumor-specific T cells, marked by CXCL13 expression, can predict how well a patient will respond to immune checkpoint blockade, highlighting their importance in antitumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defined tumor antigen-specific T cells potentiate personalized TCR-T cell therapy and prediction of immunotherapy response. He, J., Xiong, X., Yang, H., et al.[2023]

Genetically engineered T lymphocytes targeting carcinoembryonic antigen (CEA) led to significant reductions in serum CEA levels (74-99%) in three patients with metastatic colorectal cancer, with one patient showing a notable regression of cancer in the lungs and liver.

All patients experienced severe transient inflammatory colitis as a dose-limiting toxicity, highlighting both the potential efficacy and the risks associated with using CEA as a target in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Parkhurst, MR., Yang, JC., Langan, RC., et al.[2023]

In a study analyzing the cytokine profiles of TCR T-cell therapy products, higher functionality of TNFα in CD8+ T cells and active phospho-STAT3 signaling were linked to better clinical responses in solid tumor treatments.

Conversely, profiles from CD4+ T-helper 2 cells were associated with poorer outcomes, suggesting that specific cytokine levels, such as IL15, Flt3-L, and CX3CL1, could serve as important biomarkers for predicting therapy effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy. Nowicki, TS., Peters, CW., Quiros, C., et al.[2023]

The study successfully engineered T cell receptors (TCRs) specific for the cancer-testis antigen PLAC1, which is commonly expressed in breast cancer, showing that these TCR-engineered T cells can effectively target and destroy PLAC1-positive breast cancer cells in laboratory settings.

In mouse models, the PLAC1 TCR-transduced CD8+ T cells significantly delayed tumor progression, suggesting that targeting PLAC1 with engineered T cells could be a promising new approach for treating breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PLAC1-specific TCR-engineered T cells mediate antigen-specific antitumor effects in breast cancer. Li, Q., Liu, M., Wu, M., et al.[2020]

Citations

1.

tscan.com

tscan.com/wp-content/uploads/2023/11/Non-clinical-development-of-T-Plex-component-TSC-200-A0201-A-natural-HPV16-E7-specific-TCR-T-cell-therapy-for-the-treatment-of-HPV16-positive-solid-2.pdf

A natural HPV16 E7-specific TCR-T cell

TSC-200-A0201 is intended for the treatment of HPV16+ HLA-A*02:01+ cancers. HPV16 is an oncogenic virus responsible for ~57% of cervical cancers and ~21% of ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05973487

NCT05973487 | A Basket Study of Customized Autologous ...

This is a multi-center, non-randomized, multi-arm, open-label, basket study evaluating the safety and preliminary efficacy of single and repeat dose regimens of ...

3.

tscan.com

tscan.com/wp-content/uploads/2024/11/Preclinical-Models-for-T-Plex-a-Customized-Multiplexed-TCR-T-Cell-Therapy.pdf

Preclinical Models for T-Plex, a Customized Multiplexed ...

On the other hand, T-Plex products were consistently able to broaden the cytotoxic activity by targeting all tumor cells. While each TCR-T component was ...

4.

jitc.bmj.com

jitc.bmj.com/content/11/Suppl_1/A413

a natural HPV16 E7-specific TCR-T cell therapy ...

TSC-200-A0201 is intended for the treatment of HPV16+ HLA-A*02:01+ cancers. HPV16 is an oncogenic virus responsible for ~57% of cervical cancers.

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2542

Initial data from a phase 1, first-in-human clinical trial for T- ...

TScan has developed T-Plex, a multiplexed cell therapy comprising two to three different TCR-Ts, chosen from a collection of TCR-Ts called the ImmunoBank.

6.

tscan.com

tscan.com/wp-content/uploads/2024/05/2024-ASGCT-Solid-Tumor-Trial-in-Progress-Final.pdf

A phase 1, first-in-human clinical trial for T-Plex, a multiplex ...

Tumors that have lost the target HLA cannot respond to TCR-T therapy, however cancer cells never lose all their HLAs. Prospective screening for ...

7.

cancer.columbia.edu

cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/phase-1-basket-study-evaluating-safety-and-feasibility-t-plex-autologous-customized-t-cell-receptor-engineered-t-cells-targeting-multiple-peptide-hla-antigens-participants-antigen-positive-locally

A Phase 1 Basket Study Evaluating the Safety and Feasibility ...

T-Plex has not yet been approved by the Food and Drug Administration (FDA). This is a first-in-human study, which means that these products have never been ...

8.

tscan.gcs-web.com

tscan.gcs-web.com/news-releases/news-release-details/tscan-therapeutics-announces-fda-clearance-investigational-new-1

TScan Therapeutics Announces FDA Clearance of ...

TSC-200-A0201 targets HPV16, which is an oncogenic virus that is responsible for approximately 57% of cervical cancers and approximately 21% of ...

9.

ir.tscan.com

ir.tscan.com/node/8356/pdf

TScan Therapeutics Announces FDA Clearance of ...

All four TCR-T cell products are designed to be used in combination with each other and are being developed under a single master clinical trial.