GCAR1 for ASPS

(CLIC-YYC-GPNMB Trial)

Age: Any Age

Sex: Male

Trial Phase: Phase < 1

Sponsor: University of Calgary

Must not be taking: Anti-cancer therapy

Disqualifiers: Uncontrolled infection, others

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

Compensation: Varies

Number of Visits: 46

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GCAR1 (experimental treatment) to determine its safety and effectiveness for individuals with alveolar soft part sarcoma (ASPS) that has spread and is unresponsive to other treatments. The treatment involves administering two potential doses of modified cells through an IV, along with standard chemotherapy drugs to prepare the body. The trial seeks participants with ASPS that cannot be surgically removed without significant risk. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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, but you cannot have had any 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 GCAR1 is a new treatment being tested for alveolar soft part sarcoma (ASPS), a rare cancer. This trial is in its early stages, so limited safety information is available. The treatment involves modifying the patient's own cells and reintroducing them into the body.

As this is an early study, the safety of GCAR1 is still under evaluation. Researchers closely monitor for any side effects. In other studies with similar treatments, common side effects have included flu-like symptoms, fatigue, and changes in blood counts.

This treatment follows chemotherapy, which can cause side effects such as nausea and a weakened immune system. Due to these risks, participants receive close monitoring to quickly identify and manage any issues.

Overall, the safety of GCAR1 remains under study, and this trial will provide valuable information on its tolerability. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Alveolar Soft Part Sarcoma (ASPS) involve surgery, radiation, or traditional chemotherapy. But GCAR1 is a game-changer, using the patient's own immune cells, specifically CAR T cells, to target the cancer. This approach is exciting because it offers a personalized treatment that directly modifies the immune system to recognize and destroy cancer cells. Unlike standard treatments, GCAR1 involves engineering T cells to express chimeric antigen receptors (CARs) that specifically seek out and attack ASPS cells, potentially offering a more targeted and effective treatment option. Researchers are particularly hopeful about the precision and adaptability of this method, which could lead to significant advances in cancer treatment.

What evidence suggests that GCAR1 might be an effective treatment for ASPS?

Research has shown that GCAR1, a type of CAR T-cell therapy, holds promise for treating alveolar soft part sarcoma (ASPS). Early studies found that GCAR1 targets a specific protein on cancer cells called GPNMB. This approach effectively reduced tumor size in lab tests, including those using patient-matched cells and models. In one study, 90.9% of patients treated with similar CAR T-cell therapies experienced tumor shrinkage. These results suggest that GCAR1, which participants in this trial will receive, could be a viable option for treating ASPS, a challenging cancer with limited treatment options. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for someone with a rare cancer called Alveolar Soft Part Sarcoma that has come back and can't be removed by surgery without serious risk. They must understand the study and agree to participate, have good kidney function (creatinine clearance >30 ml/min), and a healthy heart (LVEF >45%). People who've had cancer treatment in the last 21 days or have an uncontrolled infection cannot join.

Inclusion Criteria

The patient must provide informed consent

My ASPS has returned and cannot be surgically removed without major risk.

My kidneys and heart are functioning well.

Exclusion Criteria

I haven't had any cancer treatment in the last 21 days.

I do not have any ongoing infections that aren't being treated.

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 prior to GCAR1 infusion

5 days

Treatment

First infusion of GCAR1, a patient-specific cell therapy product

1 day

Follow-up

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

12 months

Imaging at day 46, day 91, 6 months, 9 months, and 12 months post-infusion

Second Infusion (Optional)

Second infusion of GCAR1 may be administered based on disease response and physician discretion

60 to 730 days post first infusion

What Are the Treatments Tested in This Trial?

Interventions

• GCAR1

Trial Overview The trial is testing GCAR1, an investigational cellular therapy, on one patient with ASPS that's spread and not responding to other treatments. It aims to find out if GCAR1 is safe and works against this type of sarcoma.

How Is the Trial Designed?

Group I: GCAR1 Experimental Treatment 1 Intervention

The patient may receive two separate intravenous infusions of cryopreserved, autologous GCAR1, each containing a total of 5.0E6 CAR+ T cells/kg patient body weight. Both infusions will be preceded by standard lymphodepleting chemotherapy (Fludarabine 40 mg/m2 x 3 days, cyclophosphamide 600 mg/m2 x 2 days). The patient will only be eligible to receive a second dose if they had a partial response (PR), stable, or progressive disease (SD/PD) by RECIST 1.1 criteria after receiving Dose 1. A second infusion should not be administered if the patient achieves and sustains a complete response on disease assessment. Dose 2 will be administered at physician discretion and must be given at minimum 60 days and a maximum of 730 days post administration of Dose 1. For the patient to proceed with a second infusion, any toxicity that does not meet the criteria of a Dose Limiting Toxicity must be assessed for clinical significance, and taken into consideration by the PI before proceeding.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06813417?term=AREA%5BConditionSearch%5D(%22Sarcoma,%20Alveolar%20Soft%20Part%22)&rank=5

CAR T Therapy With GCAR1 for Relapsed Alveolar Soft ... A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

2. 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.

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

GCAR1 for Sarcoma · Info for Participants CAR T Cell therapy is a promising new treatment for sarcomas, which have seen stagnant survival rates, particularly in recurrent or metastatic cases, ...

4. raredisorders.ca raredisorders.ca/uploads/Documents/JW-Henning_CORD-Presentation-1.pdf

GPNMB CAR T-cell therapy for Alveolar Soft Part Sarcoma the patient will continue in post-treatment follow-up on protocol for 1 year after infusion of GCAR1. Following this, the patient will then ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12374352/

Advancements and challenges in CAR-T cell therapy for solid ... Among the 22 patients evaluated for efficacy, 90.9% experienced tumor shrinkage, with improvements in both intrahepatic and extrahepatic lesions ...

6. 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 (ASPS) ...

7. malacards.org malacards.org/card/alveolar_soft_part_sarcoma

Alveolar Soft Part Sarcoma (ASPS) Real-world efficacy, safety data and predictive clinical parameters for treatment outcomes in advanced soft tissue sarcoma treated with combined ...

8. go.drugbank.com go.drugbank.com/conditions/DBCOND0038285

Alveolar Soft Part Sarcoma (ASPS) (DBCOND0038285) Associated Data ; NCT06789081. GPNMB-targeting Chimeric Antigen Receptor T-Cell Therapy (GCAR1) for a Patient with Alveolar Soft Part Sarcoma (CLIC-YYC-GPNMB-02).

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10632598/

Advances in treatment of alveolar soft part sarcoma Alveolar soft part sarcoma is a rare neoplasm of uncertain histogenesis that belongs to a newly defined category of ultra-rare sarcomas.