GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma and Metastatic Retinoblastoma
NCT ID: NCT05650749
Last Updated: 2025-10-21
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
45 participants
INTERVENTIONAL
2023-05-23
2030-01-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Dose Escalation Arm
The dose escalation arm will determine the maximum tolerated dose of GPC2 CAR T cells using a standard 3+3 trial design.
GPC2 CAR T cells
The GPC2 CAR T investigational product is comprised of autologous human T cells that have been genetically modified to express a GPC2-targeting chimeric antigen receptor (CAR) transgene.
Dose Expansion Arm
If at least one dose from the dose expansion arm is determined to be safe, additional patients will be enrolled to the dose expansion arm to preliminarily evaluate the rate of response to GPC2 CAR T cells and further characterize the safety profile of GPC2 CAR T cells.
GPC2 CAR T cells
The GPC2 CAR T investigational product is comprised of autologous human T cells that have been genetically modified to express a GPC2-targeting chimeric antigen receptor (CAR) transgene.
Interventions
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GPC2 CAR T cells
The GPC2 CAR T investigational product is comprised of autologous human T cells that have been genetically modified to express a GPC2-targeting chimeric antigen receptor (CAR) transgene.
Eligibility Criteria
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Inclusion Criteria
2. Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low- or intermediate-risk, but then reclassified as high-risk are also eligible.
3. Patients must have a previously histologically confirmed diagnosis of neuroblastoma:
1. That is recurrent/relapsed or refractory/persistent according to INRC (see Section 21.1) AND
2. For which standard curative measures do not exist or are no longer effective.
3. patients at first relapse are eligible as no known curative therapies exist for relapsed high-risk neuroblastoma.
4. Patients must have evaluable or measurable disease at enrollment.
5. In addition, patient must have experienced at least one of the following:
a. New disease site documented on at least one of the following: i. 123I-meta-iodobenzylguanidine (MIBG) or 18F-mFBG (meta-fluorobenzylguanidine) scan; OR ii. CT/MRI; OR iii. FDG or Ga-68 Dotatate PET (in patients known to have MIBG non-avid tumor) and MRI findings consistent with tumor (i.e., bone lesions), OR iv. Biopsy confirmed neuroblastoma for any new or progressing lesion. b. Greater than 20% increase in a least one dimension of soft tissue mass documented by CT/MRI and a minimum absolute increase of 5 mm in longest dimension in existing lesion(s). Previously irradiated lesions may be included.
c. Bone marrow biopsy shows progressive disease according to the revised INRC (refer to Table 17) d. Stable persistent disease, such that response at the completion of upfront therapy or salvage therapy is less than partial response AND has a biopsy of at least one site showing viable neuroblastoma.
e. Responding persistent disease, defined as at least a partial response to frontline therapy (i.e., at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT/MRI, or bone marrow aspirations/biopsies). Patients in this category are required to have histologic confirmation of viable neuroblastoma from at least one residual site (tumor seen on routine bone marrow morphology is sufficient).
6. Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60 (See Table 13)
7. Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age.
8. Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease)
9. Aspartate aminotransferase (AST) ≤ 2.5 ULN (exception: AST ≤ 5 x ULN for patients with liver metastases).
10. Alanine aminotransferase (ALT) ≤ 2.5 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).
11. Patients must have a baseline pulse oximetry of at least 92% on room air. In addition, a DLCO ≥ 60% (corrected for anemia) is required if PFTs are clinically appropriate as determined by the treating investigator.
12. Left ventricular shortening fraction (LVSF) ≥28% or ejection fraction (LVEF) ≥ 50% confirmed by Echo, or adequate ventricular function documented by a scan or a cardiologist.
1. Patient age ≥ 6 months.
2. Patients must have metastatic retinoblastoma according to International Retinoblastoma Staging System (IRSS) risk classification (4) at the time of study enrollment:
a. Retinoblastoma Cohort 1 (Extra-CNS metastasis) i. Stage IVa disease ii. Extra-CNS disease must be confirmed as retinoblastoma by histology (either at diagnosis or recurrence) iii. Measurable disease: Defined as \> 1cm2 or biopsy-proven bone marrow disease iv. Prior treatment: Recurrent or refractory disease following treatment with COG ARET0321-like or equivalent regimen as part of upfront or recurrent therapy b. Retinoblastoma Cohort 2 (CNS disease) i. Stage IVb disease ii. Histologic confirmation is not required iii. CNS disease defined as measurable disease \>1cm2, non-measurable, or CSF positivity alone c. Prior treatment: i. Stage IVb.1 and IVb.2: Recurrent after treatment with COG ARET0321-like or equivalent regimen as part of upfront or recurrent therapy (see appendix 21.2) i. Stage IVb.3: Prior treatment is not required (i.e., eligible at initial diagnosis or recurrence) (see appendix 21.2)
3. Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60 (See Table 13)
4. Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN .
5. Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease)
6. Aspartate aminotransferase (AST) ≤ 2.5 ULN (exception: AST ≤ 5 x ULN for patients with liver metastases).
7. Alanine aminotransferase (ALT) ≤ 2.5 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).
8. Patients must have a baseline pulse oximetry of at least 92% on room air. In addition, a DLCO ≥ 60% (corrected for anemia) is required if PFTs are clinically appropriate as determined by the treating investigator.
9. Left ventricular shortening fraction (LVSF) ≥28% or ejection fraction (LVEF) ≥ 50% confirmed by Echo, or adequate ventricular function documented by a scan or a cardiologist.
Exclusion Criteria
2. Patients with HIV infection.
3. Patients with uncontrolled active infection.
4. Patients with primary or acquired immunodeficiency disorder.
5. Patients with a known hypersensitivity to DMSO.
6. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
7. Patients with actively progressing CNS metastases, including parenchymal or leptomeningeal involvement. (Note: CNS imaging at screening is only required if the there is a clinical indication of suspected CNS metastasis)
8. Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and/or neurotoxicity.
9. Patients with congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis.
10. Patients who have received any live vaccines within 30 days prior to enrollment.
11. Patients who are pregnant or nursing (lactating).
12. Patients who have a life expectancy \< 6 months at time of consent.
1. Patients with active hepatitis B or active hepatitis C.
2. Patients with HIV infection.
3. Patients with uncontrolled active infection.
4. Patients with primary or acquired immunodeficiency disorder.
5. Patients with a known hypersensitivity to DMSO.
6. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
7. Active medical disorder that, in the opinion of the investigator, would substantially increase the risk to the subject.
8. Patients with congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis.
9. Patients who have received any live vaccines within 30 days prior to enrollment.
10. Patients who are pregnant or nursing (lactating).
11. Patients who have a life expectancy \< 6 months at time of consent.
12. Retinoblastoma Cohort 1 (Extra-CNS disease):
1. Concurrent CNS disease (they may be eligible for Retinoblastoma Cohort 2)
2. Stage III disease (orbital or lymph node regional extension without other hematogenous metastases).
13. Retinoblastoma Cohort 2 (CNS disease):
1. "Bulky" disease (\>5 cm in diameter) within or compressing the brainstem or thalamus. Note: Tumors touching the brainstem/thalamus without evidence of compression and/or tumors in other CNS locations do not have a maximal size criterion.
2. Evidence of increased intracranial pressure.
1 Year
ALL
No
Sponsors
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Children's Hospital of Philadelphia
OTHER
Gilead Sciences
INDUSTRY
University of Pennsylvania
OTHER
National Cancer Institute (NCI)
NIH
Kite, A Gilead Company
INDUSTRY
Stephan Grupp MD PhD
OTHER
Responsible Party
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Stephan Grupp MD PhD
Chief, Cell Therapy and Transplant Section Director, Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy Medical Director, Cell and Gene Therapy Lab
Principal Investigators
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Lisa Wray, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital of Philadelphia
Locations
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Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Countries
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Central Contacts
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Facility Contacts
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CART Nurse Navigator
Role: primary
Melissa Varghese, M.S.
Role: backup
References
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Giudice AM, Matlaga S, Roth SL, Gladney W, Groff D, Hofmann TJ, Pascual-Pasto G, McIntyre B, Zecchino V, Martinez D, Spear TT, Wolpaw AJ, Assenmacher CA, Radaelli E, Pogoriler J, Pawel B, Barrett D, Grupp SA, Maris JM, Bosse KR. D3-GPC2-directed CAR T cells are safe and efficacious in preclinical models of neuroblastoma and small cell lung cancer. Clin Cancer Res. 2025 Sep 30. doi: 10.1158/1078-0432.CCR-25-0089. Online ahead of print.
Other Identifiers
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22CT012
Identifier Type: OTHER
Identifier Source: secondary_id
22-019659
Identifier Type: -
Identifier Source: org_study_id