CAR-T Cell Therapy for Solid Cancer

Overseen By Aung Naing, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunotherapy, Steroids

Disqualifiers: CNS metastases, Autoimmune disease, 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

117 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IVS-3001, a type of CAR-T cell therapy, for individuals with certain solid tumors that have not responded well to previous treatments. The trial focuses on assessing the treatment's safety, how the body processes it, and its effectiveness against cancer. Participants should have HLA-G positive tumors and have found previous treatments ineffective. This study targets those who have exhausted standard treatment options and seek new possibilities. As a Phase 1 trial, the research aims to understand 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 must stop taking your current medications. However, certain immunotherapies and systemic chronic steroid therapies are not allowed, and any ongoing toxicities from prior treatments must be resolved to a certain level. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that IVS-3001 is likely to be safe for humans?

Research shows that IVS-3001, a type of CAR-T cell therapy, targets and destroys cancer cells with a specific marker called HLA-G. In earlier studies with patients who have advanced HLA-G-positive solid tumors, IVS-3001 showed promise.

Although still in early testing stages, initial results suggest the treatment is generally well-tolerated. Some patients experienced mild side effects, while serious side effects were less common. This Phase 1/2a trial primarily aims to ensure the treatment's safety and effectiveness. Researchers closely monitor safety and watch for any unexpected reactions.

This treatment is new and not yet widely used, so more studies are needed to fully understand its safety. However, early data offers hope that IVS-3001 could be a safe option for those with HLA-G-positive solid tumors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about IVS-3001 because it uses CAR-T cell therapy to target solid cancers, which is a cutting-edge approach compared to traditional treatments like surgery, chemotherapy, and radiation. Most treatments for solid tumors focus on removing or shrinking the tumors directly, but CAR-T cell therapy works by reprogramming a patient's own immune cells (T cells) to recognize and attack cancer cells. This personalized and precise mechanism could potentially lead to more effective and longer-lasting responses, offering hope for patients who have limited options with existing therapies.

What evidence suggests that IVS-3001 might be an effective treatment for solid cancer?

Research shows that IVS-3001, a type of CAR-T cell therapy, may help fight solid tumors with a specific marker called HLA-G. In animal studies, these CAR-T cells found the tumors and destroyed cancer cells with the HLA-G marker. This suggests that IVS-3001 might also reduce tumors in humans. While CAR-T cell treatments have proven effective for blood cancers, this represents a newer approach for solid tumors. In this trial, participants will receive IVS-3001, and researchers are closely monitoring early patient results to determine if similar benefits occur. ^{1 2 3 6 7}

Who Is on the Research Team?

Aung Naing, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced HLA-G-positive solid tumors that have not responded to standard treatments can join this trial. They must be in good enough health, with a life expectancy over 12 weeks and an ECOG performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants need adequate organ function and agree to use effective birth control if applicable.

Inclusion Criteria

My tumor shows HLA-G expression.

I am fully active or can carry out light work.

I have a stored tissue sample from before my treatment.

Exclusion Criteria

I have had another type of cancer, but it's an exception.

I have previously received CAR T cell or similar therapy.

I have not received a live virus vaccine in the last 6 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive IVS-3001 to determine safety, tolerability, and the recommended phase 2 dose

8-12 weeks

Phase 2a Treatment

Participants receive IVS-3001 to evaluate anti-tumor activity in selected HLA-G+ solid tumor types

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IVS-3001

Trial Overview The trial is testing IVS-3001, a new type of CAR-T cell therapy targeting HLA-G on tumor cells. It's given after chemotherapy drugs Fludarabine and Cyclophosphamide prepare the body (lymphodepletion). The study will assess safety, how the body processes the treatment (pharmacokinetics), and its effectiveness against different types of solid tumors.

How Is the Trial Designed?

Group I: Dose Escalation (Part 1) and Expansion (Part 2 ) Experimental Treatment 4 Interventions

Participants will receive IVS 3001 at the selected dose Participants will receive IVS 3001 at the recommended phase 2 dose

IVS-3001 is already approved in United States for the following indications:

Approved in United States as IVS-3001 for:

• Renal Cell Carcinoma (RCC)
• Locally advanced or metastatic solid tumors that are HLA-G positive

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Invectys

Industry Sponsor

Trials

5

Recruited

260+

Published Research Related to This Trial

HLA-G is an immune checkpoint molecule that helps tumors evade the immune system by suppressing anti-tumor responses, making it a potential target for cancer immunotherapy.

Current clinical trials are exploring the use of monoclonal antibodies against HLA-G in combination with other immune checkpoint inhibitors like PD-1 and CTLA-4, showing promise for enhancing anti-tumor immune responses and improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-G and Other Immune Checkpoint Molecules as Targets for Novel Combined Immunotherapies. Morandi, F., Airoldi, I.[2022]

In clear-cell renal-cell carcinoma (ccRCC) patients, CD8+ T lymphocytes expressing the HLA-G receptor ILT2 were found to be more mature and exhibited higher cytotoxicity compared to other T cell subsets, suggesting they could be a valuable target for immunotherapy.

HLA-G expression on tumor cells specifically inhibited the cytotoxic activity of CD8+ILT2+ T cells, indicating that targeting the HLA-G/ILT2 checkpoint could enhance the effectiveness of existing immune therapies, especially in patients who do not respond to PD-1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD8+PD-1-ILT2+ T Cells Are an Intratumoral Cytotoxic Population Selectively Inhibited by the Immune-Checkpoint HLA-G. Dumont, C., Jacquier, A., Verine, J., et al.[2020]

This study provides the first in vivo evidence that HLA-G expression in tumor cells helps them evade the immune system by promoting the expansion of suppressor cells and altering the balance of immune responses, which allows tumors to grow in immunocompetent hosts.

Blocking HLA-G function with a specific antibody was shown to inhibit tumor development in vivo, suggesting a promising new therapeutic strategy for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of HLA-G in tumor escape through expansion of myeloid-derived suppressor cells and cytokinic balance in favor of Th2 versus Th1/Th17. Agaugué, S., Carosella, ED., Rouas-Freiss, N.[2021]

CAR T-cell therapy is a promising treatment for patients with aggressive B-cell malignancies, as it genetically modifies T-cells to specifically target and attack cancer cells.

However, this treatment can lead to severe side effects, such as cytokine release syndrome (CRS) and neurotoxicity (ICANS), necessitating the involvement of medical emergency teams for effective management and intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy and critical care : A survival guide for medical emergency teams. Messmer, AS., Que, YA., Schankin, C., et al.[2021]

HLA-G expression in tumors is associated with poor clinical outcomes in certain cancers like breast, esophageal, gastric, and hepatocellular carcinoma, suggesting it may play a role in tumor immune evasion.

However, the relationship between HLA-G expression and clinical outcomes is inconsistent across different cancer types, indicating that HLA-G may not universally function as an immune checkpoint molecule affecting tumor-immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Critical Assessment of the Association between HLA-G Expression by Carcinomas and Clinical Outcome. van de Water, RB., Krijgsman, D., Houvast, RD., et al.[2021]

Invariant Natural Killer T (iNKT) cells, which are important for anti-tumor immunity, can be inhibited by the human immune checkpoint molecule HLA-G, affecting their ability to secrete cytokines after activation.

Human dendritic cells expressing HLA-G (DC-10) were less effective at activating iNKT cells compared to those without HLA-G, suggesting that HLA-G may contribute to the limited efficacy of iNKT cell-based cancer therapies in humans compared to mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of iNKT Cells by the HLA-G-ILT2 Checkpoint and Poor Stimulation by HLA-G-Expressing Tolerogenic DC. Wu, CL., Caumartin, J., Amodio, G., et al.[2021]

CAR T-cell therapy is a promising treatment for various cancers, including hematological malignancies and solid tumors, but it can lead to serious adverse reactions such as cytokine release syndrome (CRS) and neurotoxicity.

Understanding the mechanisms behind these adverse reactions is crucial for early identification and effective treatment, which is essential for the safe clinical application of CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reactions Related to CAR-T Cell Therapy. Miao, L., Zhang, Z., Ren, Z., et al.[2021]

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]

CAR-T cell therapies, while effective for treating relapsed or refractory blood cancers, can lead to serious adverse effects such as cytokine release syndrome (CRS) and neurotoxicity, which complicate patient management.

The review discusses the pathophysiology and management strategies for these adverse events, and highlights ongoing research aimed at modifying CAR-T cells to reduce toxicity and improve patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies. Yang, C., Nguyen, J., Yen, Y.[2023]

CAR-T therapy has shown significant success in treating relapsed/refractory B-cell malignancies, utilizing genetically modified T-cells to target and eliminate cancer cells effectively.

Despite its efficacy, CAR-T therapy is associated with serious toxicities such as cytokine release syndrome and neurotoxicity, necessitating improved safety measures, especially as the therapy is being tested in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building safety into CAR-T therapy. Peters, DT., Savoldo, B., Grover, NS.[2023]

CAR T cell therapy, particularly targeting the CD19 protein, has shown significant success in treating pediatric and young adult acute lymphoblastic leukemia and diffuse large B cell lymphoma, leading to FDA approval due to durable responses in patients who did not respond to standard treatments.

Despite early successes in blood cancers, CAR T cell therapy has not yet demonstrated consistent clinical efficacy in solid tumors, highlighting the need for ongoing research to overcome challenges in the solid tumor microenvironment and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy of Non-hematopoietic Malignancies: Detours on the Road to Clinical Success. Long, KB., Young, RM., Boesteanu, AC., et al.[2020]

CAR T cell therapy has revolutionized the treatment of blood cancers like leukemia and lymphoma, but its effectiveness in solid tumors has been significantly lower due to various challenges.

Key obstacles for CAR T cell therapy in solid tumors include the lack of unique tumor antigens, difficulties in T cell movement to tumor sites, tumor diversity, and a highly immunosuppressive environment, prompting ongoing research to enhance its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of CAR T cells for solid tumors: Lessons learned and future directions. Bagley, SJ., O'Rourke, DM.[2020]

CAR T cell therapy has shown great promise in treating blood cancers, but its effectiveness against solid tumors has faced significant challenges due to issues like antigen diversity and a suppressive tumor environment.

The review highlights that the tumor microenvironment can hinder T cell function and growth, making it difficult for CAR T cells to infiltrate and effectively target solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Immunotherapy Beyond Haematological Malignancy. Hupperetz, C., Lah, S., Kim, H., et al.[2022]

The novel CAR-NK strategy targeting HLA-G effectively kills various solid tumor cells, including breast, brain, pancreatic, and ovarian cancers, and improves survival in mouse models, indicating its potential as a powerful immunotherapy.

Combining this anti-HLA-G CAR-NK therapy with low-dose chemotherapy enhances tumor targeting by increasing HLA-G expression, leading to greater tumor destruction both in vitro and in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting human leukocyte antigen G with chimeric antigen receptors of natural killer cells convert immunosuppression to ablate solid tumors. Jan, CI., Huang, SW., Canoll, P., et al.[2022]

CAR T-cell therapy has shown great promise in treating blood cancers but faces significant challenges when applied to solid tumors, such as breast cancer, due to issues like poor T cell trafficking and an immunosuppressive tumor environment.

Current research is focused on developing strategies to improve the effectiveness of CAR T-cells in solid tumors, aiming to overcome the limitations that have hindered their success in these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-T cells immunotherapy for targeting breast cancer. Rahimmanesh, I., Khanahmad, H.[2021]

Citations

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Safety and efficacy of HLA-G–targeted CAR T cells (IVS- ... Safety and efficacy of HLA-G–targeted CAR T cells (IVS-3001) in patients with advanced HLA-G–positive solid tumors: Clinical trial in progress.

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Targeted CAR-T Cells IVS-3001 In Subjects With ... The proposed clinical study is a Phase 1/2a trial to investigate the safety, tolerability, pharmacokinetics and clinical activity of anti-HLA-G CAR-T cells ...

3. invectys.com invectys.com/products-pipeline/ivs-3001-anti-hla-g-car-t-cells/

IVS-3001 : anti-HLA-G CAR T cells IVS-3001 has demonstrated in vivo its ability to migrate to tumor sites and destroy HLA-G-bearing cells. Mice treated with anti-HLA-G CAR-T cells have shown a ...

4. vjoncology.com vjoncology.com/video/yhuvawfiq3s-phase-iiia-trial-of-ivs-3001-a-hla-g-targeting-car-t-cell-therapy-in-solid-tumors/

ASCO 2025 | Phase I/IIa trial of IVS-3001, a HLA-G-targeting ... The study assesses safety, pharmacokinetics, and early efficacy in patients with previously treated, advanced HLA-G–positive solid tumors. IVS- ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11083689/

State of the Art in CAR-T Cell Therapy for Solid Tumors Chimeric antigen receptor (CAR)-T cell therapy has proven to be a powerful treatment for hematological malignancies.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05672459?cond=ovarian+cancer&aggFilters=status%3A%2Cphase%3A

A Safety And Efficacy Study Of HLA-G- Targeted CAR-T ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2022-0261.html

A phase 1/2A, safety and efficacy study of HLA-G-targeted ... A phase 1/2A, safety and efficacy study of HLA-G-targeted CAR-T cells IVS-3001 in subjects with previously treated advanced HLA-G-positive solid tumors.