NKG2D.Zeta-NK + CAR-T Cells for Bone Cancer

Overseen By Martha Arredondo

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Immunosuppressive drugs

Disqualifiers: Autoimmune, Brain metastases, Pregnancy, others

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

Compensation: Varies

Number of Visits: 8

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to combat advanced bone cancers like neuroblastoma and osteosarcoma that express GD2. It combines two types of genetically modified immune cells, NK cells and T cells, to better target and attack cancer cells. Specifically, the trial uses i15.NKG2D.zeta-NK cells and C7R.GD2.CAR-T cells. The goal is to determine the highest safe dose and assess how long these cells remain active in the body. Patients eligible for this trial have cancer that has returned or not responded to other treatments, and they can identify if their condition involves neuroblastoma or osteosarcoma that did not improve with standard care. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering patients the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are currently taking immunosuppressive drugs, except for low-dose corticosteroids.

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

Research has shown that C7R.GD2.CAR-T cells have been safe in past studies. These studies found that patients generally tolerated this treatment well, with no serious side effects limiting the dose. Some patients experienced mild side effects, such as temporary nerve issues, but these were not severe.

For i15.NKG2D.zeta-NK cells, less specific safety data is available on their own. However, NK cells are generally considered safe in many cancer treatments. Combining these cells with C7R.GD2.CAR-T cells aims to enhance treatment effectiveness and safety by helping the cells persist longer in the body.

As this is an early-phase trial, it focuses on identifying the safest dose levels. While some safety information is available, the trial continues to confirm how well these treatments are tolerated when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for bone cancer, which often involve chemotherapy and radiation, the combination of i15.NKG2D.zeta NK cells and C7R.GD2.CAR-T cells introduces a novel approach. These treatments harness the power of the immune system, with CAR-T cells engineered to specifically target and destroy cancer cells. Moreover, the NKG2D.zeta NK cells are designed to enhance the immune response, potentially boosting the effectiveness of the CAR-T cells. Researchers are excited because this dual-action strategy could offer a more precise attack on cancer cells, leading to fewer side effects and possibly better outcomes for patients.

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

Research has shown that a type of immune cell called IL-15-induced NK cells can effectively attack and destroy osteosarcoma cells, even those resistant to chemotherapy. These NK cells are specially modified to live longer and function better in the body. Studies have found that adding certain genes to these cells helps them persist and fight cancer more effectively.

In this trial, participants will receive a combination of i15.NKG2D.zeta NK cells and C7R.GD2.CAR-T cells. The GD2-targeted CAR-T cells have shown promise in treating neuroblastoma and osteosarcoma by recognizing GD2, a marker found on many cancer cells, and attacking them. By combining these NK and CAR-T cells, the treatment aims to leverage the strengths of both cell types, potentially offering a stronger defense against these hard-to-treat cancers. ^{1 3 5 6 7}

Who Is on the Research Team?

Leander D Timothy, MD

Principal Investigator

Baylor College of Medicine

Shoba A Navai, MD

Principal Investigator

Baylor College of Medicine

Stephanie L Fetzko, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with neuroblastoma or osteosarcoma that has returned after treatment or didn't respond to standard therapies. The cancer must have a substance called GD2 on its cells. There's no current standard treatment for these advanced cancers, and participants should not have received certain prior treatments.

Inclusion Criteria

I can care for myself but may need occasional help.

Informed consent and assent obtained from parent/guardian and child

My osteosarcoma has not improved or has returned after standard treatment.

Exclusion Criteria

History of hypersensitivity to murine protein-containing products

Known presence of Human Anti-Mouse Antibodies (HAMA)

Pregnancy or lactation / will not use birth control methods

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive i15.NKG2D.zeta-NK cells followed by C7R.GD2.CAR-T cells

5 days

Daily visits for infusions and monitoring

Initial Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Weekly visits for the first 4 weeks, then bi-weekly

Long-term Follow-up

Participants are monitored for long-term safety and effectiveness

15 years

Every 3 months for the first year, every 6 months for the next 4 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• C7R.GD2.CAR-T cells
• i15.NKG2D.zeta-NK cells

Trial Overview The study tests the largest safe dose of i15.NKG2D.zeta-NK cells combined with C7R.GD2.CAR-T cells in patients, how long they stay in the blood, and their effect on cancer. These genetically modified immune cells are designed to recognize and fight cancer more effectively.

How Is the Trial Designed?

Group I: i15.NKG2D.zeta NK cells and C7R.GD2.CARTs cells Experimental Treatment 1 Intervention

Three dose levels will be evaluated. This is a dose escalating trial which will infuse doses of i15.NKG2D.zeta NK cells followed by a fixed dose of C7R.GD2.CAR T cells 5 days later.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07211737

NKG2D.Zeta-NK Cell Conditioning With C7R.GD2.CAR-T ... The purpose of this study is to find the largest safe dose of i15.NKG2D.zeta-NK cells in combination with C7R.GD2.CAR-T cells ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10766856/

Current status and future challenges of CAR-T cell therapy for ... These results indicate that GD2-targeted CAR-T cell therapy may have potential in multiple drug combinations for osteosarcoma, with broad ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02019

Phase I Trial of GD2.CART Cells Augmented With ... The C7R-GD2.CART cohort developed grade 1 tumor inflammation–associated neurotoxicity in seven of eight (88%) cases, controllable with anakinra.

4. spandidos-publications.com spandidos-publications.com/10.3892/ijo.2024.5628

Chimeric antigen receptor T cells in the treatment ... The present review focused on the advances in the development of CAR‑T cells to improve their clinical efficacy, and discussed ways to overcome ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2212137424001155

The efficacy and applicability of chimeric antigen receptor ... Osteosarcoma, Ewing's sarcoma, and chondrosarcoma are estimated to have around 53.9 %, 50.6 %, and 75.2 % 5-year survival, respectively [6]. This chance of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11097842/

Safety and biological outcomes following a phase 1 trial of ... Here, we report the safe administration of third-generation, GD2-specific autologous CAR-T cell therapy to 12 patients with metastatic GD2- ...

7. cell.com cell.com/cancer-cell/fulltext/S1535-6108(23)00403-8

GD2-CAR T cells in patients with osteosarcoma and ... The infusions of GD2-CAR T cells were safe; no dose-limiting toxicities were detected and 15.4% (2/13) patients experienced grade 1 cytokine ...