GCAR1 for Sarcoma

(SPS-Q2 Trial)

Age: Any Age

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Calgary

Disqualifiers: Uncontrolled infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: 7

Duration: 6-7 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called GCAR1 for alveolar soft part sarcoma (ASPS). The goal is to determine if GCAR1 is safe and effective for patients whose ASPS has returned and isn't responding to standard treatments. The trial administers two doses of GCAR1 through IV infusions, with a break of a few months in between. This might suit someone whose ASPS has recurred and who maintains good organ function. As an Early Phase 1 trial, this research focuses on understanding how GCAR1 works in people, offering patients the opportunity to be among the first to receive this new treatment.

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

The trial information does not specify if you need to stop taking your current medications. However, you cannot have had anti-cancer therapy within 21 days before starting the trial treatment.

Is there any evidence suggesting that GCAR1 is likely to be safe for humans?

Research shows that treatments like GCAR1, including larotrectinib and entrectinib, usually cause mild side effects. Common side effects include dizziness and pain. Another study on a patient with a similar type of cancer found that a related treatment was well-tolerated and helped maintain disease stability for six months. Although specific information on GCAR1 remains limited, these findings suggest it might be relatively easy to tolerate. However, since this trial is in the early stages, the researchers are still gathering safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for sarcoma, which often involve surgery, radiation, and chemotherapy, GCAR1 is an innovative approach that uses the patient's own modified immune cells to target cancer. Researchers are excited about GCAR1 because it is a CAR T-cell therapy, which means it leverages the body's immune system by engineering T cells to specifically recognize and attack cancer cells. This personalized cell-based therapy could potentially offer more precise targeting of cancer cells with fewer side effects compared to traditional treatments. The ability to escalate doses within the same patient also allows for a more tailored approach to treatment, potentially enhancing its effectiveness against sarcoma.

What evidence suggests that GCAR1 might be an effective treatment for alveolar soft part sarcoma?

Research has shown that GCAR1, a new type of therapy, targets a protein called GPNMB found on some cancer cells. Early lab studies indicate that GCAR1 can attack and destroy cancer cells, including those from patients and in lab-grown models. This suggests it might work against a rare cancer called alveolar soft part sarcoma (ASPS) that has GPNMB. Although limited information exists from human studies, these early results provide a scientific basis for its potential to treat ASPS. Participants in this trial will receive GCAR1 in an intrapatient two-dose escalation study, with each dose preceded by standard lymphodepleting chemotherapy. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with a rare cancer called Alveolar Soft Part Sarcoma (ASPS) that has come back after treatment. They must be healthy enough in terms of kidney function and heart strength, not have active infections, and can't be pregnant or breastfeeding. Also, they should not have had any cancer treatments in the last 3 weeks.

Inclusion Criteria

The patient must provide informed consent

My kidneys and heart are functioning well.

Exclusion Criteria

I do not have any ongoing infections that aren't under control.

Pregnancy or nursing

I haven't had cancer treatment in the last 3 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Standard lymphodepleting chemotherapy with Fludarabine and Cyclophosphamide before each GCAR1 infusion

5 days

Treatment

Two-dose escalation study with intravenous infusions of GCAR1, with at least three months between infusions

6-7 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with diagnostic imaging at specified intervals

1 year

5 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• GCAR1

Trial Overview The study is testing GCAR1, a CAR T therapy designed to target ASPS cells that show GPNMB on their surface. It's an experimental approach being tried out on one patient to see if it's safe and works better than current treatments for this relapsed cancer.

How Is the Trial Designed?

Group I: GCAR1 Experimental Treatment 1 Intervention

This is an intrapatient two-dose escalation study. The patient will receive two separate intravenous infusions of cryopreserved, autologous GCAR1, with at least three months (+/- 30 days) between infusions. Both infusions will be preceded by standard lymphodepleting chemotherapy (Fludarabine 40 mg/m2 x 3 days, cyclophosphamide 600 mg/m2 x 2 days) . Dose 1 will be 5.0E6 CAR+ T cells/kg patient body weight, Dose 2 will be 2.5E7 CAR+ T cells/kg patient body weight. Infusions will be intravenous, single infusions.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Alberta Health Services, Calgary

Collaborator

Trials

15

Recruited

2,600+

Alberta Precision Laboratories

Collaborator

Published Research Related to This Trial

CAR T Cell therapy is a promising new treatment for sarcomas, which have seen stagnant survival rates, particularly in recurrent or metastatic cases, highlighting the urgent need for novel therapies.

Recent studies have identified several sarcoma-associated antigens suitable for CAR T Cell targeting, such as HER2 and GD2, showing encouraging results and suggesting that this therapy could improve outcomes for sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications. Thanindratarn, P., Dean, DC., Nelson, SD., et al.[2020]

A study analyzing 1568 reported cases of ocular adverse effects (OAEs) from BRAF and MEK inhibitors found that BRAF monotherapy is significantly linked to various eye issues, including iris and ciliary body abnormalities and anterior uveitis, indicating a need for careful monitoring of these side effects.

MEK inhibitor monotherapy was associated with retinal and choroid abnormalities, and the combination therapy of BRAF and MEK inhibitors showed potential for increased ocular toxicity, suggesting that personalized management strategies are necessary for patients undergoing combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular Safety Profile of BRAF and MEK Inhibitors: Data from the World Health Organization Pharmacovigilance Database. Mettler, C., Monnet, D., Kramkimel, N., et al.[2021]

In a study of 466 metastatic renal cell carcinoma (mRCC) patients treated between 2007 and 2011, 85.8% experienced at least one adverse event (AE), with fatigue, vomiting, and diarrhea being the most common.

The study revealed that younger patients (<65 years) had higher rates of AEs compared to older patients, highlighting the importance of closely monitoring and managing AEs in real-world settings, as their frequency and severity can differ from those reported in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of "Real-World" data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice. Hirsch, BR., Harrison, MR., George, DJ., et al.[2021]

A systematic review of 26 studies on multi-targeted kinase inhibitors for advanced cancer revealed that common side effects include diarrhea, fatigue, nausea, and hypertension, affecting more than 10% of patients.

While adverse events are frequent with multi-kinase inhibitors, serious side effects are less common compared to traditional cytotoxic cancer therapies, indicating a potentially safer profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of multi-targeted kinase inhibitors as monotherapy treatment of cancer: a systematic review of the literature. Crean, S., Boyd, DM., Sercus, B., et al.[2019]

Larotrectinib and entrectinib, first-generation TRK inhibitors, are effective first-line treatments for advanced non-small cell lung cancer (NSCLC) with TRK gene fusions, showing rapid and long-lasting clinical benefits.

A safety analysis of 807 reports revealed that the most common adverse reactions were dizziness and pain, with no significant long-term safety concerns noted, indicating a favorable risk-benefit profile for these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety Profiles of Two First-Generation NTRK Inhibitors: Analysis of Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS) Database. Liguori, V., Gaio, M., Zinzi, A., et al.[2023]

A machine-learning model was developed using data from 4638 patients across 16 FDA-approved small molecule kinase inhibitors (SMKIs) to analyze the relationship between kinase targets and adverse events (AEs), providing a new tool for predicting safety risks in cancer treatments.

The model not only helps identify potential kinase-inhibitor adverse event pairs but also serves as a precision medicine tool to enhance patient safety by forecasting clinical safety signals and aiding in the development of safer SMKI therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. Gong, X., Hu, M., Liu, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07104682?tab=table

A Study to Determine the Safety and Effectiveness ... 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 ...

2. withpower.com withpower.com/trial/phase-sarcoma-2025-3a296

GCAR1 for Sarcoma · Info for Participants A single patient study to determine whether GCAR1 is safe and effective for re-treatment of alveolar soft part sarcoma (ASPS) with GPNMB surface expression that ...

3. medrxiv.org medrxiv.org/content/10.1101/2025.02.26.24319604v1.full-text

Development and first-in-human CAR T therapy against the ... We developed a GPNMB-targeting CAR T therapy called GCAR1 that shows activity against patient-matched cells, organoids and xenograft models.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12026197/

Review of Adoptive Cellular Therapies for the Treatment of ... The estimated overall 3-year survival for sarcoma was found to be 38%, and 5-year survival was 14%. D'Angelo et al. later reported on a pilot ...

5. ctv.veeva.com ctv.veeva.com/study/a-study-to-determine-the-safety-and-effectiveness-of-the-investigational-cellular-therapy-gcar1-in-a

A Study to Determine the Safety and Effectiveness of the ... A single patient study to determine whether GCAR1 is safe and effective for refractory, progressive metastatic alveolar soft part sarcoma ...

6. research.ucalgary.ca research.ucalgary.ca/participate/open-label-individual-patient-study-investigating-safety-and-efficacy-gcar1-patient-metastatic-hrebacc-25-0218

An Open Label Individual Patient Study Investigating the ... This study is intended to understand if a new cancer therapy called GCAR1 is safe and effective in treating patients with metastatic cancer. Eligibility.

7. trial.medpath.com trial.medpath.com/clinical-trial/54a5fcffc6f1c0ec/nct06789081-gpnmb-car-t-cell-therapy-alveolar-soft-part-sarcoma

GPNMB-targeting Chimeric Antigen Receptor T-Cell Therapy ... Safety profile adverse events CAR T cell therapy solid tumors sarcoma management strategies ... Outcome data and publication updates. Subscribe. Free ...