CAR-GPC3 T Cell Therapy for Cancer

(DUET-1 Trial)

Not currently recruiting at 7 trial locations

Overseen By Richard Kapsa

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sotio Biotech Inc.

Must not be taking: Antineoplastics, Corticosteroids

Disqualifiers: CNS tumors, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 23

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, BOXR1030 (also known as CAR-GPC3 T Cell Therapy), for individuals with certain advanced cancers that exhibit high levels of the protein glypican-3 (GPC3). The goal is to determine the appropriate dose and assess safety following a specific type of chemotherapy. It targets patients with advanced liver cancer, lung cancer, liposarcoma, or Merkel cell carcinoma who have not found success with other treatments. Eligible participants have tumors expressing GPC3 and have experienced disease progression or intolerance to standard treatments. As a Phase 1 trial, this research aims to understand how the treatment functions in people, offering participants the chance to be among the first to receive this new therapy.

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

The trial requires a washout period for certain medications before starting treatment. You may need to stop some medications, especially antineoplastic treatments, for a specific time before the trial begins. It's best to discuss your current medications with the trial team to understand what changes might be necessary.

Is there any evidence suggesting that BOXR1030 T Cell Therapy is likely to be safe for humans?

Research shows that BOXR1030 is a new treatment being tested for safety in people with advanced solid tumors that have a protein called glypican-3 (GPC3). This treatment involves modifying T cells, a type of immune cell, to find and attack cancer cells with GPC3.

As BOXR1030 is being tested in humans for the first time, the main goals are to determine the right dose and identify any side effects. Since testing is in its early stages, there is limited information on how well people tolerate BOXR1030 or what side effects might occur. However, reaching this stage suggests that earlier lab studies and tests showed enough promise to warrant human trials.

Early trials aim to find the safest way to administer a new treatment and observe how the body reacts, so participants receive close monitoring throughout the process. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for GPC3+ solid tumors, which often include traditional chemotherapy or surgery, BOXR1030 is a type of CAR-T cell therapy. This innovative approach engineers a patient's own T cells to specifically attack cancer cells expressing the GPC3 protein. Researchers are excited about BOXR1030 because it offers a targeted treatment, potentially leading to fewer side effects and improved effectiveness compared to conventional options. Additionally, CAR-T therapies have shown promise in other cancer types, fueling hope for significant advancements in treating GPC3+ tumors.

What evidence suggests that BOXR1030 T Cell Therapy might be an effective treatment for GPC3+ solid tumors?

Research has shown that BOXR1030, the treatment under study in this trial, has promising results in early studies. This treatment targets GPC3, a protein often found in certain aggressive solid tumors. Compared to other treatments aimed at GPC3, BOXR1030 T cells reduced tumor growth more effectively in animal tests. These results suggest that BOXR1030 might effectively treat cancers with high levels of GPC3. While more research is needed to confirm its effectiveness in humans, the early data is encouraging. ^{1 2 3 6 7}

Who Is on the Research Team?

Pauline Duhard, Pharm.D.

Principal Investigator

SOTIO Biotech AG

Are You a Good Fit for This Trial?

Adults aged 18-80 with advanced solid tumors positive for GPC3, such as liver cancer or lung squamous cell carcinoma. They must have a life expectancy over 16 weeks, good organ function, and no severe complications like major untreated brain metastasis. Women of childbearing age and men with partners must agree to effective contraception.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and tests show high levels of GPC3.

My liver cancer is not fibrolamellar or mixed hepatocellular cholangiocarcinoma.

I may have had radiation for symptom relief or hormone treatment, but it's been over a week since.

Exclusion Criteria

I have a heart condition that affects my daily life.

I do not have severe diseases like uncontrolled bleeding, serious infections, or active hepatitis.

I have untreated brain tumors or metastasis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Eligible subjects undergo leukapheresis to obtain T cells for BOXR1030 manufacturing

1 week

Lymphodepleting Chemotherapy

Subjects receive a 3-day LD chemotherapy regimen with fludarabine and cyclophosphamide

1 week

Treatment

Subjects receive BOXR1030 administration and remain hospitalized for 10 days post-infusion

4 weeks

Inpatient stay for 10 days post-infusion

Post-treatment Evaluation

Subjects are monitored for safety and effectiveness with regular visits and assessments

6 months

Daily visits for the first week, then weekly visits up to 6 months

Long-term Follow-up

Subjects are monitored for long-term safety and disease status for up to 15 years

15 years

Visits at Months 7, 9, 11, 13, 15, 18, 21, 24, every 6 months until Year 5, then annually

What Are the Treatments Tested in This Trial?

Interventions

• BOXR1030

Trial Overview The trial is testing BOXR1030 T Cells after chemotherapy in patients with GPC3-positive tumors. It's the first time this treatment is being used on humans (Phase 1), aiming to find the safest dose for Phase 2 trials while monitoring its safety across multiple centers.

How Is the Trial Designed?

Group I: GPC3+ solid tumors Experimental Treatment 1 Intervention

One time intravenous administration of BOXR1030 after completion of cyclophosphamide and fludarabine LD chemotherapy

Who Is Running the Clinical Trial?

Sotio Biotech Inc.

Lead Sponsor

Trials

2

Recruited

150+

SOTIO, LLC

Lead Sponsor

Trials

1

Recruited

110+

SOTIO Biotech a.s.

Industry Sponsor

Trials

3

Recruited

270+

SOTIO Biotech AG

Industry Sponsor

Trials

5

Recruited

450+

SOTIO Biotech

Industry Sponsor

Trials

2

Recruited

150+

Published Research Related to This Trial

T cells engineered with GPC3-targeted chimeric antigen receptors (CAR) effectively kill GPC3-positive hepatocellular carcinoma (HCC) cells in vitro, demonstrating a strong correlation between their cytotoxic activity and the level of GPC3 expression in target cells.

In vivo studies showed that third-generation GPC3-targeted CAR T cells could eradicate HCC xenografts with high GPC3 expression and significantly prolong the survival of mice with established tumors, indicating their potential as a promising treatment for GPC3-positive HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma. Gao, H., Li, K., Tu, H., et al.[2022]

In a study involving 1,926 subjects from 17 clinical trials, patients with acute lymphocytic leukemia (ALL) were found to have a higher risk of severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) compared to those with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

The use of CAR T cells produced with gammaretrovirus vectors containing CD28 sequences was linked to increased rates of sNTX, while administering cytokine-directed therapies and corticosteroids at lower toxicity grades was associated with reduced rates of sCRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. Foster, M., Negash, Y., Eberhardt, L., et al.[2022]

CAR-T cell therapy has shown remarkable success in treating B-cell malignancies, but researchers are focused on improving its safety and effectiveness due to risks like cytokine release syndrome and off-target effects.

Innovative safety strategies, such as ON- and OFF-switch CARs and multi-antigen-targeting CAR-T cells, are being developed to enhance the persistence and reduce adverse events associated with CAR-T therapy, paving the way for a new generation of treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering Next-Generation CAR-T Cells for Better Toxicity Management. Andrea, AE., Chiron, A., Bessoles, S., et al.[2023]

Chimeric-antigen-receptor T cells (CAR-T) targeting CD19 are associated with several adverse drug reactions (ADRs), with the most common being cytokine release syndrome (CRS), neurological disorders, and hematological disorders, as identified in a study analyzing 1783 safety reports.

While CAR-T therapy can lead to severe ADRs, particularly in the week following administration, the overall fatality rate from these reactions is relatively low at 5.5%, though serious conditions like hemophagocytic-lymphohistiocytosis and infections require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. Dolladille, C., Ederhy, S., Ezine, E., et al.[2021]

The fourth-generation GPC3-targeted CAR-T cells (GPC3-BBZ-7×19) demonstrated enhanced proliferation and chemotactic abilities compared to second-generation CAR-T cells, indicating a potentially more effective treatment for hepatocellular carcinoma (HCC).

In vivo studies showed that GPC3-BBZ-7×19 CAR-T cells significantly eliminated GPC3-positive HCC tumors in immunodeficient mice, suggesting they could provide a durable and effective therapeutic option for HCC in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Construction and function of Glypican-3-targeted fourth-generation chimeric antigen receptor T cells (secreting IL-7 and CCL19)]. Huang, W., Liu, Y., Hu, Y., et al.[2020]

The study engineered CAR-T cells that can express IL-12, which significantly enhances their ability to target and destroy GPC3+ tumor cells, showing improved efficacy in both laboratory and animal models.

Inducible IL-12 expression not only boosts the antitumor response but also reduces regulatory T cell infiltration, suggesting a safer profile for CAR-T therapy, making it a promising option for patients who cannot undergo traditional lymphodepletion chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Armored Inducible Expression of IL-12 Enhances Antitumor Activity of Glypican-3-Targeted Chimeric Antigen Receptor-Engineered T Cells in Hepatocellular Carcinoma. Liu, Y., Di, S., Shi, B., et al.[2020]

CDR3δ-grafted γ9δ2T cells, developed from genetically modified peripheral blood lymphocytes, show strong antitumor activity against ovarian epithelial carcinoma and cervical adenocarcinoma in vitro and in vivo, indicating their potential as a promising immunotherapy.

These modified γ9δ2T cells can produce cytokines and effectively kill tumor cells, demonstrating significant antitumor effects in animal models, which supports their candidacy for clinical applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDR3δ -grafted γ9δ2T cells mediate effective antitumor reactivity. Zhao, H., Xi, X., Cui, L., et al.[2021]

T cells engineered with GPC3-specific CARs demonstrated strong cytotoxic effects against various solid tumors, including hepatocellular carcinoma and malignant rhabdoid tumors, indicating their potential as an effective treatment option.

Among the different CAR constructs tested, the GBBz CAR showed superior T cell expansion and a Th1-biased cytokine profile, suggesting it may be the most promising candidate for further clinical development in treating GPC3-positive solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity. Li, W., Guo, L., Rathi, P., et al.[2022]

Glypican 3 (GPC3) is expressed in 66.3% of lung squamous cell carcinoma (LSCC) samples, making it a promising target for therapy, as it is rarely found in normal lung tissues.

CARgpc3 T cells, engineered to target GPC3, showed strong antitumor activity by effectively eliminating GPC3-positive LSCC cells in vitro and in two xenograft models, suggesting they could be a novel treatment option for LSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy using T lymphocytes redirected to glypican-3 for the treatment of lung squamous cell carcinoma. Li, K., Pan, X., Bi, Y., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05120271

BOXR1030 T Cells in Subjects With Advanced GPC3- ... This is a first-in-human (FIH), Phase 1/2, open-label, multicenter study to assess safety and determine the recommended Phase 2 dose (RP2D) of BOXR1030 ...

2. isrctn.com isrctn.com/ISRCTN15110275

Cell therapy clinical trial of BOXR1030 in GPC3 positive ... This study is to test the safety of giving BOXR1030 to participants with cancer expressing GPC3. It will test BOXR1030, referred to as a chimeric antigen ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9067639/

BOXR1030, an anti-GPC3 CAR with exogenous GOT2 ... Compared to control GPC3 CAR alone, BOXR1030 (GPC3-targeted CAR T cell that co-expressed GOT2) demonstrated superior in vivo efficacy in aggressive solid tumor ...

4. biorxiv.org biorxiv.org/content/10.1101/2021.11.17.469041v1.full-text

BOXR1030, an anti-GPC3 CAR with exogenous GOT2 ... Compared to T cells expressing CAR alone, BOXR1030 T cells demonstrated superior in vivo efficacy and have favorable attributes including ...

5. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2021-0939.html

A First-in-Human, Phase 1/2, Dose Escalation Study of ... Study #2021-0939. A First-in-Human, Phase 1/2, Dose Escalation Study of BOXR1030 T cells in Subjects With Advanced GPC3-Positive Solid Tumors.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-02422

BOXR1030 T Cells in Subjects With Advanced GPC3- ... This is a first-in-human (FIH), Phase 1/2, open-label, multicenter study to assess safety and determine the recommended Phase 2 dose (RP2D) of BOXR1030 ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT462474

DUET-01: A first-in-human, phase 1/2 study of BOXR1030 ... BOXR1030 is an autologous T-cell therapy that co-expresses a chimeric antigen receptor (CAR) targeting GPC3 on tumor cells and glutamic-oxaloacetic transaminase ...