CD30 CAR T-Cells for Testicular Cancer

Overseen By Catherine Cheng

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with Nonseminomatous Germ Cell Tumors (NSGCT), a type of testicular cancer. The goal is to determine if ATLCAR.CD30 cells, a form of CAR T-cell therapy, can be detected in the body and how long they persist. These cells combine T cells, which fight infections, and antibodies, which protect the body, to potentially create a more effective cancer treatment. Individuals with NSGCT who have tried at least one other treatment but still experience growing or returning tumors might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ATLCAR.CD30 cells, a type of CAR T-Cell therapy, have been tested in patients with lymphomas and are safe. These cells combine T cells and antibodies to better target cancer cells. In earlier studies, patients tolerated this treatment well, experiencing manageable side effects. Most side effects were mild to moderate, such as fever or tiredness.

Serious side effects were less common but included low blood cell counts or infections, typical for treatments affecting the immune system. Since this study is in a phase focusing more closely on safety and effectiveness, earlier research has already demonstrated a good safety record for the therapy. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for testicular cancer, which often include chemotherapy and radiation, ATLCAR.CD30 is a novel approach that uses genetically engineered T-cells to specifically target cancer cells. This treatment is exciting because it involves CAR T-cell therapy, where a patient's own immune cells are modified to better recognize and attack cancer cells marked by the CD30 protein. By focusing on this unique target, ATLCAR.CD30 has the potential to offer a more precise and less toxic treatment option, potentially leading to fewer side effects and improved outcomes for patients with nonseminomatous germ cell tumors.

What evidence suggests that ATLCAR.CD30 Cells could be an effective treatment for testicular cancer?

Research has shown that CD30 CAR T-Cells, which participants in this trial will receive, could help treat testicular cancer, particularly embryonal carcinomas. In lab studies, these cells have demonstrated their ability to fight cancer using human cancer cell samples. They may benefit patients with nonseminomatous germ cell tumors that have not responded to other treatments. This treatment employs T cells to destroy cancer cells and antibodies to help the immune system locate the cancer. The goal is to develop a stronger and more effective treatment by targeting the CD30 marker found on some cancer cells. ^{2 4 5 6 7}

Who Is on the Research Team?

Matthew Milowsky, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with Nonseminomatous Germ Cell Tumors (NSGCT) who've had at least one prior treatment can join. They must show tumor growth or elevated cancer markers after high-dose chemo. Pregnant women, those breastfeeding, and individuals with active HIV, HTLV, hepatitis B or C are excluded.

Inclusion Criteria

My cancer is a type of germ cell tumor that is not seminoma.

I have had at least one treatment for my non-seminoma germ cell tumor.

My cancer has returned or worsened after strong chemotherapy.

Exclusion Criteria

I do not have active HIV, HTLV, hepatitis B, or hepatitis C infections.

Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated in the study).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Administration of autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) to subjects with CD30+ Nonseminomatous Germ Cell Tumors

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of overall response rate and progression-free survival

12 weeks

Long-term Follow-up

Monitoring of overall survival and persistence of ATLCAR.CD30 in peripheral blood

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• ATLCAR.CD30 Cells
• Cyclophosphamid
• Fludarabine

Trial Overview The trial is testing ATLCAR.CD30 Cells combined with Cyclophosphamide and Fludarabine in patients with NSGCT. It's a phase 2 study to see if modified T cells from the patient's blood can fight cancer more effectively when combined with antibodies.

How Is the Trial Designed?

Group I: ATLCAR.CD30 Experimental Treatment 3 Interventions

Single Group Assignment: Subjects with Nonseminomatous Germ Cell Tumors who meet eligibility criteria for cellular therapy.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

University Cancer Research Fund at Lineberger Comprehensive Cancer Center

Collaborator

Trials

5

Recruited

150+

Published Research Related to This Trial

Human teratocarcinoma stem cells, like other pluripotent cells, can develop into various tissues, but the role of growth factors in regulating their growth is not well understood compared to mouse stem cells.

CD30 and its ligand may play a role in identifying stem cell identity and regulating embryonal carcinoma stem cells, but exogenous CD30 ligand does not promote growth in human multipotent stem cells in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD30 and its ligand: possible role in regulation of teratoma stem cells. Pera, MF., Bennett, W., Cerretti, DP.[2019]

CD19-targeted CAR T cell therapy has shown remarkable efficacy, achieving complete remission in 70-90% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL), highlighting its potential as a powerful treatment for B cell malignancies.

The ongoing phase I study using a non-viral gene transfer method (piggyBac-transposon system) for CD19 CAR T cell therapy in pediatric and young adult patients indicates a promising direction for expanding treatment options in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene-modified T-cell therapy using chimeric antigen receptors for pediatric hematologic malignancies. Nakazawa, Y.[2017]

CD30-redirected CAR T cells (CD30.CAR T cells) effectively target and kill embryonal carcinoma (EC) cells in vitro and in vivo, demonstrating their potential as a treatment for aggressive testicular germ cell tumors.

These CAR T cells not only attack CD30+ tumor cells but also eliminate surrounding CD30- cells through a mechanism involving Fas/FasL interactions, suggesting a strategy to overcome tumor heterogeneity and enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30+ and CD30- Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions. Hong, LK., Chen, Y., Smith, CC., et al.[2020]

CD30 is a promising target for cancer treatment because it is highly expressed in tumors but has low levels in healthy tissues, making therapies that target it potentially safer and more effective.

Various therapeutic strategies have been developed against CD30, including monoclonal antibodies and CAR-T cell therapies, which show promise in treating lymphoid neoplasms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD30 as a therapeutic target in adult haematological malignancies: Where are we now? Veyri, M., Spano, JP., Le Bras, F., et al.[2023]

In a phase 1 study involving 12 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), the autologous CD19-CAR T-cell therapy was well tolerated, with low rates of cytokine release syndrome (6 patients) and neurotoxicity (3 patients).

75% of the patients achieved a minimal residual disease-negative complete response in the bone marrow, although higher disease burden before treatment was linked to more side effects and lower response rates, emphasizing the importance of pre-infusion disease status on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Talleur, AC., Qudeimat, A., Métais, JY., et al.[2022]

CD30 mRNA was found in all 9 cases of embryonal carcinoma (EC) or mixed germ cell tumors with an EC component, indicating that CD30 is a specific marker for these types of testicular neoplasms.

The presence of soluble CD30 in the serum of patients with EC suggests it could be a useful biomarker for monitoring the disease, as it was detected in all tested patients with EC but not in most patients with other testicular germ cell tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD30 antigen in embryonal carcinoma and embryogenesis and release of the soluble molecule. Latza, U., Foss, HD., Dürkop, H., et al.[2022]

Chimeric antigen receptor (CAR) T-cell therapy has shown success in phase 1 clinical trials for targeting and killing tumor cells, but safety concerns like on-target/off-tumor effects and cytokine release syndrome necessitate strategies to mitigate these risks.

Current research is exploring various methods to enhance the safety of CAR T-cell therapy, including pharmacologic therapies, suicide genes, and innovative approaches to restrict cytotoxic effects specifically to cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seatbelts in CAR therapy: How Safe Are CARS? Minagawa, K., Zhou, X., Mineishi, S., et al.[2022]

Brentuximab vedotin, a targeted therapy that effectively kills cancer cells expressing CD30, shows promise in treating testicular germ cell tumors (TGCTs), particularly in patients with advanced disease who have limited treatment options.

The study found that brentuximab vedotin works well in combination with certain chemotherapy drugs like etoposide and paclitaxel, but not with cisplatin, which may limit its use in standard treatment regimens for TGCTs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of brentuximab vedotin, alone or in combination with current clinical therapies, in the treatment of testicular germ cell tumors. Yeste-Velasco, M., Guo, T., Mao, X., et al.[2020]

CAR T cells have shown significant clinical effectiveness in treating blood cancers, but their success in solid tumors has been less impressive, highlighting the need for further research in this area.

While CAR T cell therapy can lead to serious side effects like cytokine release syndrome and neurological toxicity, some theoretical risks have not yet been observed in clinical settings, emphasizing the importance of managing known toxicities for safe treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and management in CAR T-cell therapy. Bonifant, CL., Jackson, HJ., Brentjens, RJ., et al.[2023]

The study demonstrates that CD30-targeted CAR-T cell therapy is effective in treating recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL), showing significant tumor suppression in both laboratory and mouse model experiments.

The engineered 9C11-2 CAR T cells exhibited strong cytotoxic effects against CD30-positive cancer cells, indicating their potential as a promising therapeutic option for patients with this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb. Wu, Y., Chen, D., Lu, Y., et al.[2022]

CAR T cell therapy targeting CD19 can effectively treat B cell malignancies but poses safety risks by also destroying healthy B cells that express the same antigen, leading to potential long-term tissue damage.

Research suggests that targeting activation-associated antigens, which are only temporarily present on stem cells, is safer than targeting lineage-associated antigens, which can harm tissue stem cells during their maturation process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells? Hombach, AA., Abken, H.[2017]

In a study of 72 patients with extranodal natural killer/T-cell lymphoma (NKTCL), 56% of cases were found to express CD30, which was associated with better responses to non-anthracycline-based therapies.

CD30 positivity, particularly at a cutoff value of 5%, was linked to longer overall survival in patients treated with non-anthracycline chemotherapy, suggesting that CD30 could serve as a valuable prognostic factor and therapeutic target in NKTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic implications of CD30 expression in extranodal natural killer/T-cell lymphoma according to treatment modalities. Kim, WY., Nam, SJ., Kim, S., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-2-non-seminomatous-germ-cell-tumors-10-2022-cb00b

CD30 CAR T-Cells for Testicular Cancer The available research shows that CD30 CAR T-Cells have demonstrated antitumor activity against embryonal carcinomas, a type of testicular cancer.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10135

Genetically Engineered Cells (ATLCAR.CD30) for the ... ATLCAR.CD30 cells may be effective at treating patients with refractory or relapsed nonseminomatous germ cell tumors.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9968831/

Immune checkpoint inhibitors and Chimeric Antigen ... In this article, we will analyze the molecular mechanisms underlying the immune action in the development of GCTs, and we will report the data ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7590161/

CD30-Redirected Chimeric Antigen Receptor T Cells Target ... We found that CD30-redirected CAR T cells (CD30.CAR T cells) exhibit antitumor activity in vitro against the human EC cell lines Tera-1, Tera-2 and NCCIT.

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/autologous-cd30car-cd28-cd3zeta-expressing-t-lymphocytes

Clinical Trials Using Autologous CD30CAR-CD28- ... Genetically Engineered Cells (ATLCAR.CD30) for the Treatment of Patients with Refractory or Relapsed CD30+ Nonseminomatous Germ Cell Tumors. Status: Active.

6. careacross.com careacross.com/clinical-trials/trial/NCT05634785

CD30 CAR for CD30+ NSGCT This study is designed to combine both T cells and antibodies to create a more effective treatment called autologous T lymphocyte chimeric antigen receptor ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05634785

NCT05634785 | CD30 CAR for CD30+ NSGCT This study is designed to combine both T cells and antibodies to create a more effective treatment called autologous T lymphocyte chimeric antigen receptor ...