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

Official title

A Phase I Study of GCAR1, a Chimeric Antigen Receptor (CAR) T-CELL Therapy for Participants With Selected Relapsed/Refractory GPNMB-Expressing Solid Tumours

Overview

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

Detailed description

GCAR1 is a type of CAR-T cell therapy that is designed to identify a protein (GPNMB) that is present on the cells of certain types of cancer. Laboratory tests have shown that GCAR1 helps the immune system recognize cancer cells and may help slow down cancer growth.

The purpose of this study is to find out what effects the new treatment, GCAR1 has on certain cancers. This study will test increasing doses of GCAR1 in participants with alveolar soft part sarcoma (ASPS), triple negative breast cancer (TNBC), and renal cell carcinoma (RCC) expressing high levels of the GPNMB protein, to establish recommended doses for further testing.

Interventions

• Drug Fludarabine
  Assigned at enrollment
• Drug Cyclophosphamide
  Assigned at enrollment
• Biological GCAR1
  Dose escalation

Primary outcome measures

• 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 [Time frame: 3 years]

Secondary outcome measures (3)

• Number and severity of adverse eventsGCAR1 utilizing CTCAE v5.0 [Time frame: 3 years]
• Overall response rate utilizing RECIST 1.1 [Time frame: 3 years]
• Duration of response [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• 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

• Progressive disease following at least one line of systemic treatment for metastatic disease which must include an ADC (all participants) and an ICI (participants whose tumours express PD-L1).
• ≤3 lines of treatment for metastatic disease.
• Must have had at least 1 prior line of cytotoxic chemotherapy for breast cancer, in any setting, which must have included an anthracycline and a taxane (unless contraindicated).
• RCC - must have progressive disease following at least one line of systemic treatment for metastatic disease that must have included an ICI and a VEGFR targeted agent (unless contraindicated).
• Participants must have recovered to ≤ grade 1 from all reversible toxicity related to prior therapies.
• Adequate washout must be followed per protocol.
• Previous major surgery is permitted ≥21 days prior to enrollment
• Prior external beam radiation is permitted ≥28 prior to enrollment. Concurrent radiotherapy is not permitted.
• Adequate hematologic and biochemical parameters.
• Consent and assent, when applicable, must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant or their parent/ legal guardian (if applicable) must sign a consent form prior to screening onto the trial to document their willingness to participate.
• Fit for leukapheresis and has adequate venous access for cell collection.
• Must be accessible for treatment and follow up at the participating centre for a minimum of 12 months or for as long as is deemed necessary by the treating physician.
• Participants of childbearing potential must have agreed to use a highly effective contraceptive method.

Exclusion criteria

• 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.
• Active intracerebral metastases or leptomeningeal disease. Participants who have received definitive treatment, are clinically stable and do not require corticosteroids are eligible to participate in the trial.
• Pregnant or breastfeeding women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 2 centers

• Arthur J.E. Child Comprehensive Cancer Centre — Calgary
• University Health Network — Toronto

Identifiers

NCT: NCT07297667 · I246

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗