HER2 CAR-T Therapy for Advanced Solid Tumors

Recruiting at 17 trial locations

Overseen By Fate Trial Disclosure

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fate Therapeutics

Must not be taking: CNS medications

Disqualifiers: Pregnancy, Cardiovascular disease, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-9 weeks

351 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called FT825, a type of CAR-T therapy, for individuals with advanced solid tumors unresponsive to standard therapies. Researchers aim to determine if FT825 is safe and effective in shrinking tumors, either alone or with cetuximab. Participants are divided into two groups: one receiving only FT825 and the other receiving FT825 with cetuximab. Individuals with advanced HER2-expressing or EGFR-expressing tumors who have not found success with other treatments may be suitable for this study. As a Phase 1 trial, this research seeks to understand how FT825 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking medications for non-malignant CNS diseases like stroke or epilepsy, you must not have taken them within 2 years prior to joining the study.

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

Research has shown that FT825, also known as ONO-8250, is generally safe for people with solid tumors. In earlier studies, patients tolerated low doses of FT825 well, with manageable side effects. This treatment specifically targets cancer cells with a protein called HER2.

Researchers are also examining the safety of FT825 in combination with Cetuximab, another cancer drug that targets a different protein, EGFR. Although detailed safety information for this combination is not yet available, it is under close monitoring to ensure safety.

As this is a phase 1 trial, the main goal is to assess the safety and tolerability of the treatment. This phase represents the early stage of testing in humans, so more data is being collected. However, early results for FT825 alone appear promising. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about HER2 CAR-T therapy for advanced solid tumors because it represents a novel approach compared to traditional treatments like chemotherapy and targeted therapies. Unlike these standard options, which often target the tumor environment or growth factors, HER2 CAR-T therapy uses engineered T cells to specifically seek out and destroy cancer cells expressing the HER2 protein. This precision targeting could potentially lead to more effective tumor reduction with fewer side effects. Additionally, the combination of FT825 with cetuximab in some participants targets both HER2 and EGFR proteins, offering a dual-action approach that may enhance treatment efficacy against tumors expressing multiple growth factors.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that FT825, also known as ONO-8250, yields promising results in targeting tumors with the HER2 protein, often found in certain cancers. In earlier studies, FT825 effectively targeted cancer cells with varying HER2 levels, from high to low. This targeting aims to minimize harm to healthy cells, a common issue with similar treatments. In this trial, one group of participants will receive FT825 alone, while another group will receive FT825 combined with cetuximab, a type of antibody. Early evidence suggests that this combination could enhance treatment outcomes for individuals with advanced solid tumors expressing the EGFR protein. ^{1 2 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Fate Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with advanced HER2-positive or other solid tumors. Participants must have measurable disease and be able to receive chemotherapy. They should not have had previous CAR-T therapy, active infections, or any medical conditions that could interfere with the study.

Inclusion Criteria

Anticipated life expectancy of at least 3 months

My cancer is advanced or has spread, confirmed by tests.

I am using birth control as required by local laws for clinical study participants.

Exclusion Criteria

I am not pregnant or breastfeeding.

My organs are not functioning properly.

I have or had an autoimmune disease or immune deficiency.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive chemotherapy prior to the administration of FT825 or FT825 + Cetuximab

4 weeks

Treatment

Participants receive FT825 or FT825 + Cetuximab in Cycle 1, each cycle is approximately 61 days

8-9 weeks

Retreatment

Based on safety and clinical benefit, participants may receive an additional treatment cycle (Cycle 2)

8-9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• FT825/ONO-8250

Trial Overview The trial is testing FT825 (ONO-8250), a new type of CAR-T cell therapy, combined with standard chemotherapy drugs. Some participants will also receive monoclonal antibodies. The study has two parts: first to find the right dose and then to see how well it works in specific tumor types.

How Is the Trial Designed?

Group I: Regimen B: FT825 + Cetuximab Experimental Treatment 7 Interventions

Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).

Group II: Regimen A: FT825 Experimental Treatment 6 Interventions

Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).

Who Is Running the Clinical Trial?

Fate Therapeutics

Lead Sponsor

Trials

22

Recruited

1,200+

Published Research Related to This Trial

The chA21-4-1BBz CAR T cells demonstrated a strong ability to target and kill HER2 overexpressing gastric cancer cells in laboratory tests, showing a Th1 skewed cytokine response that correlates with HER2 levels on tumor cells.

In animal models, these CAR T cells significantly reduced tumor size and improved survival in mice with HER2 overexpressing tumors, while not affecting tumors with low HER2 expression, indicating a targeted and potentially safer treatment approach for gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effects and persistence of a novel HER2 CAR T cells directed to gastric cancer in preclinical models. Han, Y., Liu, C., Li, G., et al.[2020]

Genetically modified NK-92 cells expressing a chimeric antigen receptor targeting the ErbB2 (HER2/neu) antigen can specifically kill tumor cells that overexpress this marker, which is common in many epithelial tumors.

These NK-92-scFv(FRP5)-zeta cells maintain their safety profile by not affecting normal human cells and demonstrate enhanced cytotoxicity against resistant ErbB2-expressing tumors, indicating their potential for effective cell-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction. Uherek, C., Tonn, T., Uherek, B., et al.[2021]

The engineered T1E28z chimeric antigen receptor effectively activates T cells against various tumor cells by targeting multiple ErbB receptor combinations, demonstrating its potential for broad application in cancer therapy.

In mouse models with established tumors overexpressing ErbB1/2 or ErbB2/3, T1E28z⁺ T cells showed significant antitumor activity, suggesting this immunotherapeutic approach could overcome resistance seen with traditional ErbB-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flexible targeting of ErbB dimers that drive tumorigenesis by using genetically engineered T cells. Davies, DM., Foster, J., Van Der Stegen, SJ., et al.[2022]

HER2 positive JIMT-1 breast tumors are resistant to trastuzumab, but T cells engineered with a second-generation CAR targeting HER2 can effectively eliminate these resistant tumors, demonstrating their potential in overcoming trastuzumab resistance.

In SCID mice, even a small number of CAR T cells (as few as 17,500) can lead to complete remission of HER2 positive tumors, suggesting that optimizing CAR T cell dosing could enhance treatment efficacy for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Small Number of HER2 Redirected CAR T Cells Significantly Improves Immune Response of Adoptively Transferred Mouse Lymphocytes against Human Breast Cancer Xenografts. Tóth, G., Szöllősi, J., Abken, H., et al.[2020]

Chimeric antigen receptor-transduced natural killer (CAR-NK) cells offer a promising cancer immunotherapy option by providing rapid and potent cytotoxicity without the toxic side effects commonly associated with T cell therapies, such as cytokine release syndrome and graft-versus-host disease.

CAR-NK cells can be produced on a large scale as 'off-the-shelf' products, making them a practical solution for widespread clinical use in enhancing immune responses against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-NK cells for cancer immunotherapy: from bench to bedside. Zhang, L., Meng, Y., Feng, X., et al.[2022]

HER2 is commonly expressed in osteosarcoma but at low levels, making traditional HER2 monoclonal antibody treatments ineffective; however, genetically modified T cells with HER2-specific chimeric antigen receptors (CARs) can effectively target these tumors.

In mouse models, the adoptive transfer of HER2-specific T cells led to significant regression of established osteosarcoma tumors, demonstrating the potential of CAR T-cell therapy in treating cancers with low antigen expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression. Ahmed, N., Salsman, VS., Yvon, E., et al.[2021]

The newly engineered HER2-specific sPD-1-CAR-NK cells enhance the immune response against HER2-positive breast cancer by releasing bioactive soluble PD-1, which improves the cytotoxic activity of these cells against cancer targets.

In mouse models, sPD-1-CAR-NK cells demonstrated superior anticancer efficacy compared to traditional HER2-CAR-NK cells, with increased infiltration and activation of immune cells in tumor tissues and no significant side effects observed, making it a promising treatment for trastuzumab-resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering a HER2-CAR-NK Cell Secreting Soluble Programmed Cell Death Protein with Superior Antitumor Efficacy. Xia, W., Chen, J., Hou, W., et al.[2023]

In a Phase 1 study involving 21 Japanese patients with advanced solid tumors, neratinib was found to have a maximum-tolerated dose of 240 mg daily, with common side effects including diarrhea and fatigue.

The study showed that neratinib led to partial responses in 2 breast cancer patients and stable disease in several others, indicating its potential efficacy in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study. Ito, Y., Suenaga, M., Hatake, K., et al.[2022]

HER2 CAR-engineered natural killer (NK) cells significantly enhance anti-tumor activity against HER2-expressing cancer cells, showing greater cytotoxicity than traditional CAR-T cells, especially in solid tumors.

Unlike CAR-T cells, HER2 CAR-NK cells do not cause harmful effects on non-cancerous cells, making them a safer option for immunotherapy in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded human NK cells armed with CAR uncouple potent anti-tumor activity from off-tumor toxicity against solid tumors. Portillo, AL., Hogg, R., Poznanski, SM., et al.[2021]

CAR T-cell immunotherapy, which involves genetically modifying T cells to target cancer cells, has shown promising results, especially in treating B-cell malignancies with several patients achieving complete and durable responses.

Current research is expanding CAR T-cell therapy to solid tumors, specifically targeting members of the ErbB family, indicating a potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ErbB-targeted CAR T-cell immunotherapy of cancer. Whilding, LM., Maher, J.[2022]

CAR-engineered NK-92 cells targeting the ErbB2 antigen showed effective tumor cell killing in laboratory tests and maintained their antitumor activity in live models, indicating their potential for cancer treatment.

Using γ-irradiation as a safety measure can prevent the replication of these NK cells while still allowing them to effectively attack tumors, making them a promising candidate for clinical use in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Schönfeld, K., Sahm, C., Zhang, C., et al.[2021]

HER2 CAR T-cell therapy shows promise for treating solid tumors, particularly in cancers like breast cancer, but it carries significant risks of severe side effects, such as cytokine release syndrome due to targeting HER2 on non-cancerous tissues.

The review highlights ongoing efforts to enhance the safety of HER2 CAR therapies through novel designs and alternative CAR host selections, aiming to minimize the risk of toxicities while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Driving better and safer HER2-specific CARs for cancer therapy. Liu, X., Zhang, N., Shi, H.[2019]

Citations

1. ir.fatetherapeutics.com ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-highlights-cancer-selective-her2-targeting

Fate Therapeutics Highlights Cancer-selective, HER2 ... FT825 / ONO-8250 incorporates a novel H 2 CasMab-2 binding domain targeting HER2 that is designed to overcome on-target, off-tumor toxicity.

2. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A307

268 Development of FT825/ONO-8250: an off-the-shelf ... Results FT825/ONO-8250 demonstrated potent and specific CAR-based targeting of tumor target lines across HER2 expression levels (3+ to 1+) from ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12133747/

Research progress on HER2-specific chimeric antigen ... The results demonstrated that anti-PD-1 antibodies can significantly enhance the efficacy of anti-HER2 CAR-T cells against HER2-positive solid ...

4. cgtlive.com cgtlive.com/view/fate-and-ono-initiate-enrollment-her2-car-t-trial-ft825

Fate and Ono Initiate Enrollment for HER2-CAR T Trial FT825 previously demonstrated potency and specificity for HER2-expressing cancer cells in preclinical data presented at the 2023 Society for ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1934590925001870

Preferential tumor targeting of HER2 by iPSC-derived CAR ... Although effective in several hematologic settings, chimeric antigen receptor (CAR) T cells have had limited success in solid tumors. Obstacles ...

6. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A310

269 Preferential targeting of HER2-expressing cancer cells ... FT825/ONO-8250 demonstrates preferential targeting of HER2 expressed by tumor cells in both in vitro and in vivo settings.

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/457195

FT825/ONO-8250, an Off-the-Shelf, HER2 CAR-T, With or ... This is a phase 1 study designed to evaluate the safety, tolerability, and antitumor activity of FT825 (also known as ONO-8250) with or without monoclonal ...

8. ir.fatetherapeutics.com ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-announces-initiation-phase-1-clinical-trial

Fate Therapeutics Announces Initiation of Phase 1 Clinical ... “The preclinical data for FT825 / ONO-8250 indicate a highly-differentiated therapeutic profile across a broad range of solid tumors, with the ...