GCAR1, a Chimeric Antigen Receptor (CAR) T-CELL Therapy for Relapsed/Refractory GPNMB-Expressing Solid Tumours

NCT07297667 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: I246
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

Only enrolling in Canada. The purpose of this study is to identify the highest dose of GCAR1, a chimeric antigen receptor (CAR-T) cell therapy, that can be tolerated without causing very severe side effects, and to see what effects GCAR1 has on selected cancers

Conditions

Renal Cell Carcinoma; Alveolar Soft Part Sarcoma; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• To determine the recommended phase II dose (RP2D), defined as the next lower dose below the maximum administered dose, of GPNMB directed CAR T cell therapy

  (GCAR1) in participants with selected tumours (alveolar soft part sarcoma, renal cell carcinoma (excluding clear cell), triple negative breast cancer) expressing GPNMB

  3 years

Secondary Outcomes (3)

• Number and severity of adverse eventsGCAR1 utilizing CTCAE v5.0

  3 years

• Overall response rate utilizing RECIST 1.1

  3 years

• Duration of response

  3 years

Study Arms (1)

GCAR1 Infusion

EXPERIMENTAL

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: GCAR1

Interventions

Fludarabine DRUG

Assigned at enrollment

GCAR1 Infusion

GCAR1 BIOLOGICAL

Dose escalation

GCAR1 Infusion

Cyclophosphamide DRUG

Assigned at enrollment

GCAR1 Infusion

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Archival tumour specimen must be positive for GPNMB with high expression by immunohistochemistry (central laboratory testing).
• Histologically and/or cytologically confirmed diagnosis of one of the following tumours that is advanced/ metastatic/ recurrent or unresectable, for which no curative therapy exists.
• alveolar soft part sarcoma
• renal cell carcinoma (excluding clear cell)
• triple negative breast cancer (ER, PR and HER-2 negative as defined by ASCO/CAP criteria)
• Must have a formalin fixed paraffin embedded tissue block (from primary or metastatic tumour) available and must have provided informed consent for the release of the block.
• Presence of radiologically documented disease.
• Measurable disease as defined by RECIST 1.1.
• ASPS participants ≥ 15 years of age.
• TNBC and RCC participants ≥ 18 years of age.
• ECOG performance status of 0 or 1 or Karnofsky or Lansky \> 60.
• Anticipated life expectancy of ≥ 6 months.
• Must have received prior systemic therapy as shown below;
• ASPS - completed all systemic therapy available that has been shown to improve survival (unless contraindicated).
• TNBC

You may not qualify if:

• Participants on active anticancer therapy for other advanced or metastatic malignancies.
• Concurrent treatment with other anti-cancer therapy
• Prior therapy with a gene therapy product or any adoptive T cell therapy or prior GPNMB targeting therapy.
• Live attenuated vaccination administered within 30 days prior to or planned within 30 days after GCAR1 therapy.
• Primary immunodeficiency or history of severe autoimmune disease (including: Crohn's disease, rheumatoid arthritis, systemic lupus) requiring immunosuppressive agents/ systemic disease modifying agents within 2 years of enrollment.
• Active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the participant to be managed according to the protocol including but not limited to:
• Hepatitis B or C virus (HBV or HCV). For participants with previous HBV or HCV infection who are currently on treatment, they are eligible if they have an undetectable viral load via quantitative PCR and/or nucleic acid testing
• HIV positive by serology and PCR
• Uncontrolled fungal, bacterial, viral or other infection
• Current infection with HTLV-1
• Tuberculosis
• Syphilis
• West Nile Virus
• Untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac dysfunction (including cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects) or unstable angina congestive heart failure or myocardial infarction within the previous year.
• Known sensitivity or allergy to fludarabine, cyclophosphamide or any of their components, or to GCAR1 or any of its components.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• University of Calgary: collaborator
• BioCanRx: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (3)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Sarcoma, Alveolar Soft Part; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Mona Shafey

  Tom Baker Cancer Centre, Calgary, Alberta, Canada

  STUDY CHAIR

Central Study Contacts

Laura Pearce

CONTACT

613-533-6430; lpearce@ctg.queensu.ca

Mariam Jafri

CONTACT

613-533-6430; mjafri@ctg.queensu.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2025
• First Posted: December 22, 2025
• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): September 1, 2033
• Last Updated: April 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)