TCR-T Cell Therapy for Cancer

Recruiting at 1 trial location

Overseen By Tobi Adewale

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Christian Hinrichs

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunodeficiency, Severe autoimmune diseases, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest dose of a new treatment using specialized immune cells, known as KK-LC-1 TCR-T cells, for individuals with certain metastatic cancers. Researchers seek to evaluate the treatment's effectiveness and safety for participants. Individuals with gastric, lung, triple-negative breast, or cervical cancers that test positive for the protein KK-LC-1 and have not responded to standard treatments may be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in humans.

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, participants on immunosuppressive drugs, including corticosteroids, are not eligible unless they meet specific criteria. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that KK-LC-1 TCR-T cell therapy is likely to be safe for humans?

A previous study tested KK-LC-1 TCR-T cells in the lab and showed promise in targeting specific cancer cells. However, these findings remain preliminary, and further research is needed to confirm their safety for people. As a phase 1 trial, the main focus is on identifying the safest dose and monitoring for side effects.

Regarding aldesleukin, which is part of the treatment, earlier studies have shown it can be safely administered to patients with certain cancers. Some individuals may experience side effects like flu-like symptoms or low blood pressure, but these are generally manageable.

Overall, while early data on safety exists, this trial will provide more specific information about how well people tolerate this combination of treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about KK-LC-1 TCR-T cell therapy because it represents a cutting-edge approach to cancer treatment. Unlike traditional cancer therapies, which often involve chemotherapy or radiation, this treatment uses genetically modified T cells to specifically target and attack cancer cells expressing the KK-LC-1 antigen. This precision targeting could potentially lead to fewer side effects and more effective tumor destruction. Additionally, the use of aldesleukin in combination aims to boost the immune system, enhancing the therapy's overall effectiveness.

What evidence suggests that KK-LC-1 TCR-T cells might be an effective treatment for metastatic cancers?

Research has shown that KK-LC-1 TCR-T cells, which participants in this trial will receive, target a specific protein called KK-LC-1, found in some cancers. This protein belongs to a group known as cancer germline antigens, usually present in tumors but not in normal tissues. Early lab studies demonstrated that these specially designed T cells can identify and attack cancer cells with the KK-LC-1 protein. Initial results suggest that this method could effectively target and destroy these cancer cells. Although human studies have provided limited information, this approach appears promising for treating cancers with this protein. ^{6 7 8 9 10}

Who Is on the Research Team?

Christian S Hinrichs, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic gastric, breast, cervical, or lung cancer that tests positive for KK-LC-1. They must have tried standard treatments without success and be in good physical condition (ECOG 0 or 1). Participants need functioning organs/marrow and no active infections like HIV or hepatitis. Pregnant women can't join, and those who can bear children must use contraception.

Inclusion Criteria

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

It's been over 4 weeks since my last cancer treatment and any side effects are mild or stable.

I have up to 3 brain metastases treated with surgery or radiosurgery and stable for 1 month.

Exclusion Criteria

Not applicable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants receive a conditioning regimen consisting of cyclophosphamide and fludarabine

1 week

Treatment

Participants receive a single infusion of KK-LC-1 TCR-T cells followed by administration of aldesleukin

1 day

Initial Follow-up

Participants are monitored for adverse events and dose limiting toxicity to determine the maximum tolerated dose

4 weeks

Extended Follow-up

Participants are monitored for tumor response and duration of response

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Aldesleukin
• KK-LC-1 TCR-T cells

Trial Overview The trial is testing the safety and maximum dose of KK-LC-1 TCR-T cells combined with aldesleukin in treating certain cancers. It's a phase I study to see how patients tolerate this treatment and what their clinical response will be after receiving a conditioning regimen followed by the therapy.

How Is the Trial Designed?

Group I: KK-LC-1 TCR-T cells Experimental Treatment 2 Interventions

Subjects will receive a conditioning regimen, KK-LC-1 TCR-T cells, and aldesleukin.

KK-LC-1 TCR-T cells is already approved in United States for the following indications:

Approved in United States as KK-LC-1 TCR-T cell therapy for:

• Gastric cancer
• Breast cancer
• Cervical cancer
• Lung cancer

Who Is Running the Clinical Trial?

Christian Hinrichs

Lead Sponsor

Trials

3

Recruited

70+

Cancer Immunology and Metabolism Center of Excellence at Rutgers Cancer Institute of New Jersey

Collaborator

Trials

1

Recruited

30+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

T Cure Bioscience

Collaborator

Trials

1

Recruited

30+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Transducing γδT cells with a TCR specific to the KK-LC-1 lung cancer antigen demonstrated effective cytotoxic activity against lung cancer cells in vitro and inhibited tumor growth in vivo when administered shortly after cancer cell transplantation in mice.

The study found that TCRαβ-CD8 γδT cells were less effective against tumors that expressed FasL, suggesting that the interaction between FasL on cancer cells and Fas on TCRαβ-CD8 γδT cells may induce apoptosis, limiting the therapy's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of adoptive immunotherapy with KK-LC-1-specific TCR-transduced γδT cells against lung cancer cells. Ichiki, Y., Shigematsu, Y., Baba, T., et al.[2023]

The original monoclonal antibody Kmab34B3 successfully detected KK-LC-1 protein expression in 82% of gastric cancer tumor specimens, indicating its potential as a diagnostic tool for identifying cancerous cells.

Kmab34B3 also showed the ability to stain non-tumorous pyloric gland specimens, suggesting that it could be useful for detecting KK-LC-1 expression in both precancerous and cancerous stomach tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of Kita-Kyushu Lung Cancer Antigen-1 as Detected by a Novel Monoclonal Antibody in Gastric Cancer. Takahashi, Y., Fukuyama, T., Futawatari, N., et al.[2021]

Natural killer (NK) cells play a crucial role in the immune response against lung cancer, but their effectiveness can be hindered by factors such as ineffective activation and tumor-specific challenges, which limits the success of current immunotherapies.

Combining strategies to reactivate NK cells with other treatments may improve clinical outcomes for lung cancer patients, addressing the limitations of existing therapies and enhancing anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NK cell-based therapeutics for lung cancer. Pockley, AG., Vaupel, P., Multhoff, G.[2020]

The study found that the tumor-associated antigen KK-LC-1 is expressed in 81.6% of gastric cancer specimens analyzed, indicating its potential role as a cancer/testis antigen (CTA) in this type of cancer.

KK-LC-1's high expression frequency compared to other CTAs suggests it could be a promising target for immunotherapy and diagnostic purposes in gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent High Expression of Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) in Gastric Cancer. Shida, A., Futawatari, N., Fukuyama, T., et al.[2022]

A novel T cell receptor (TCR) targeting the Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) has been developed, showing effective recognition and regression of tumors expressing this antigen in preclinical models, particularly in epithelial cancers like gastric cancer.

The KK-LC-1 TCR-Ts demonstrated specificity for cancer cells without cross-reactivity to other human proteins, suggesting a potentially safe therapeutic option for treating epithelial malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1. Marcinkowski, B., Stevanović, S., Helman, SR., et al.[2021]

KK-LC-1 is overexpressed in hepatocellular carcinoma (HCC) tissues and its high levels are associated with poor survival outcomes, indicating its potential as a prognostic biomarker.

The study reveals that KK-LC-1 promotes HCC progression by enhancing cell growth, migration, and invasion through a novel signaling pathway involving presenilin-1 and the Notch1/Hes1 pathway, driven by hypomethylation of CpG islands.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypomethylation-mediated activation of cancer/testis antigen KK-LC-1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling. Chen, Z., Zuo, X., Pu, L., et al.[2021]

The study successfully transduced TCRαβ genes into γδ T cells, enabling them to specifically target and kill lung cancer cells expressing the KK-LC-1 antigen, demonstrating effective cytotoxic activity in both laboratory assays and in a mouse model.

Adoptive transfer of these genetically modified γδ T cells significantly suppressed the growth of tumors in mice, indicating that this approach could be a promising new strategy for adoptive immunotherapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of human γδ T cells transducted with CD8 and with T-cell receptors of tumor-specific cytotoxic T lymphocytes. Hanagiri, T., Shigematsu, Y., Kuroda, K., et al.[2021]

A new monoclonal antibody (clone 34B3) was developed to detect the protein expression of KK-LC-1, a cancer/testis antigen, in breast cancer samples, showing a significant difference in detection rates compared to gene expression (11.8% for gene vs. 52.9% for protein).

KK-LC-1 protein expression was found in all cases of triple-negative breast cancer (n=8) and in all tumors lacking estrogen receptor expression, suggesting its potential as a target for immunotherapy in these aggressive breast cancer subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of KK-LC-1 Protein, a Cancer/Testis Antigen, in Patients with Breast Cancer. Kondo, Y., Fukuyama, T., Yamamura, R., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31455429/

Cancer targeting by TCR gene-engineered T cells ... - PubMed We describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05483491

NCT05483491 | KK-LC-1 TCR-T Cell Therapy for Gastric, ... This study will determine the MTD of KK-LC-1 TCR-T cells for the treatment of metastatic cancers that express KK-LC-1 and will assess clinical tumor response to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9286905/

Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) This article introduces the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1), a new member of the CTA family, in different types of tumors and its ...

4. jitc.biomedcentral.com jitc.biomedcentral.com/articles/10.1186/s40425-019-0678-x

Cancer targeting by TCR gene-engineered T cells directed ... We describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05035407

NCT05035407 | T Cell Receptor Gene Therapy Targeting ... The purpose of this study is to determine the safety of different doses of KK-LC-1 TCR T cells plus aldesleukin to treat metastatic or refractory/recurrent KK- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4918260/

Update on use of aldesleukin for treatment of high-risk ... Although the overall response rate to ipilimumab in either treatment arm was low (10.9%), ipilimumab-treated patients had improved overall survival compared ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00554515

The High-Dose Aldesleukin (IL-2) "Select" Trial for Patients ... To determine, in a prospective fashion, the response rate to high-dose IL-2 for patients with metastatic renal cell carcinoma and "poor" pathologic predictive ...

8. jitc.bmj.com jitc.bmj.com/content/2/1/26

High dose interleukin-2 (Aldesleukin) - expert consensus ... This review is based upon a consensus meeting and includes guidelines on pre-treatment screening, criteria for administration and withholding doses.

9. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.3053

A retrospective analysis of high-dose aldesleukin (HD IL-2) ... Conclusions: Early patient data from the PROCLAIM database suggest that HD IL-2 is a safe treatment option for pts who have had progressive ...

10. aacrjournals.org aacrjournals.org/clincancerres/article/21/3/561/13942/The-High-Dose-Aldesleukin-Select-Trial-A-Trial-to

The High-Dose Aldesleukin “Select” Trial: A ... - AACR Journals Data presented to the FDA showed an objective response rate (ORR) of 14% in 255 patients with mRCC treated in seven phase II trials (1).