Tazemetostat+Nivo/Ipi in INI1-Neg/SMARCA4-Def Tumors

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Atypical Teratoid Rhabdoid Tumor, INI1 (SMARCB1)-Deficient Primary CNS Malignant Tumors, SMARCA4-deficient Primary CNS Malignant Tumors, Malignant Rhabdoid Tumor (MRT), Rhabdoid Tumor of the Kidney (RTK), Epithelioid Sarcoma, Chordoma

In brief

This research study involves a combination of three drugs given together as a possible treatment for malignant rhabdoid tumor, atypical teratoid rhabdoid tumor, epithelioid sarcoma, chordoma or other tumors that are deficient in one of two possible proteins, either INI-1 (SMARCB1) or SMARCA4. The names of the study drugs involved in this study are: * Tazemetostat (TAZVERIK) * Nivolumab (OPDIVO) * Ipilimumab (YERVOY)

Key facts

Study ID

NCT05407441

Run by

Susan Chi, MD

People needed

49

Starts

2023-08-10

Expected to finish

2029-02-01

Last updated by the study team

2026-04-13

Who can join

Age: 1 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Diagnosis: Histologically confirmed tumors at diagnosis or at relapse (as applicable):
• Stratum A
• Atypical Teratoid Rhabdoid Tumor (ATRT)
• Other INI1- or SMARCA4-deficient primary CNS malignant tumors (with PI approval)
• Stratum B
• Malignant rhabdoid tumor (MRT)
• Rhabdoid tumor of the kidney (RTK)
• Epithelioid sarcoma
• Chordoma (poorly differentiated or de-differentiated)
• Other INI1- or SMARCA4-deficient malignant tumors (with PI approval)
• All subjects must have had tumor assessment at original diagnosis or relapse showing either of the following: Loss of INI1 confirmed by immunohistochemistry (IHC) OR molecular confirmation of tumor bi-allelic SMARCB1 (INI1) loss or mutation when INI1 IHC is equivocal or unavailable
• Loss of SMARCA4 confirmed by IHC OR molecular confirmation of tumor SMARCA4 loss or mutation (with PI approval) Reports confirming these findings (including tumor sequencing if available) will be reviewed by the Sponsor-Investigator, PI or designee for approval of eligibility prior to enrollment.
• Treatment status: All subjects must have completed planned upfront treatment for their disease for strata A1 or B1. Subjects need not have relapsed or have refractory disease to be eligible for this protocol.
• Disease Status: For subjects under consideration for strata A1 or B1, subjects must have evaluable disease Note: Leptomeningeal lesions/disease are allowed as evaluable disease.
• For relapsed/refractory subjects under consideration for strata A2 or B2, subjects must have measurable disease as defined by RANO for stratum A2 or RECIST v1.1 for stratum B2. See Section 11.
• Note: the following do not qualify as measurable disease:
• malignant fluid collections (e.g., ascites, pleural effusions)
• bone marrow infiltration
• lesions only detected by nuclear medicine studies (e.g., bone, gallium or PET scans)
• elevated tumor markers in plasma or CSF
• previously irradiated lesions that have not demonstrated clear progression post- radiation therapy
• leptomeningeal lesions that do not meet the measurement requirements for RANO.
• For subjects under consideration for strata A3 or B3, subjects must have no evidence of evaluable or measurable disease by exam or imaging.
• Pre-recurrent subjects to be enrolled in strata A1, B1, A3, or B3 must be enrolled within 8 weeks of completion of upfront therapy
• Age ≥ 6 months and ≤ 21years of age

You may not qualify if…

• Concomitant Medications
• Subjects who are receiving any other investigational agents or other anti-cancer agents are not eligible.
• CYP3A4 Agents: Subjects who are currently receiving drugs that are strong or moderate inducers or inhibitors of CYP3A4 are not eligible. Such inducers or inhibitors of CYP3A4 are prohibited from 14 days prior to the first dose of tazemetostat to the end of the study. See Appendix C for a list of agents. Note:Dexamethasone for CNS tumors or metastases, on a stable or decreasing dose, is allowed up to 0.12mg/kg/day prednisone equivalents.
• Subjects with a known history of HIV, hepatitis B, and/or hepatitis C (testing not required as part of screening).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or any other concurrent disease which in the judgment of the Investigator would make the subject inappropriate for enrollment on this study.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are exceptions. Intermittent use of bronchodilators or local steroid injections are not excluded. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diagnoses not listed must be approved by the Principal Investigator.
• On screening CBC differential, subjects must not have any significant morphologic abnormalities concerning for MPN/MDS or ALL.
• Subjects must not have any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS) or prior history of lymphoblastic lymphoma (LBL) or leukemia (ALL).
• Subjects who have received prior solid organ transplantation are not eligible.
• Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as there is yet no available information regarding human fetal or teratogenic toxicities.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. OX40, CD137).
• Subjects who have received live / attenuated vaccine within 30 days of first dose of study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tazemetostat or Orasweet.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.

Where it is running

• Boston Children's Hospital — Boston, Massachusetts, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Texas Children's Hospital — Houston, Texas, United States

Full record on ClinicalTrials.gov

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