Phase II Study of Tazemetostat in Solid Tumors Harboring an ARID1A Mutation

NCT05023655 | Terminated Phase 2 FDA Drug

• 1 other identifier: EPZ-IST-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The FDA approved targeted agent tazemetostat inhibits EZH2 and induces durable tumor responses in patients with B-cell non-Hodgkin's lymphoma and epithelioid sarcomas. Responses have also been demonstrated in INI1 and SMARCA4 negative solid tumors patients. Since EZH2 plays a critical role in driving the biology of ARID1A mutated malignancies, we hypothesize that inhibition of EZH2 with tazemetostat will lead to significant clinical benefit in ARID1A mutated malignancies.

Conditions

Solid Tumor; ARID1A Gene Mutation

Keywords

ARID1A mutation; solid tumors; tazemetostat

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Evidence of anti-tumor activity will be assessed by objective response, as defined by RECIST 1.1. This will be used to summarize ORR (CR+PR), as well as the rates for the individual categories of response, (i.e., CR, PR, SD, and PD).

  through study completion, estimated to be 1 year after the last subject enrolled

Secondary Outcomes (1)

• Disease Control Rate

  through study completion, estimated to be 1 year after the last subject enrolled

Study Arms (1)

Tazemetostat

EXPERIMENTAL

tazemetostat 800 mg po twice daily in continuous 28- day cycles

Drug: Tazemetostat

Interventions

Tazemetostat DRUG

800mg po twice daily

Also known as: tazverik

Tazemetostat

Eligibility Criteria

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

You may qualify if:

• Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.
• Histologically and/or cytologically confirmed advanced or metastatic solid tumor harboring ARID1A mutation (except epithelioid sarcoma)
• Progression of disease following approved therapies or for which no standard therapy exists
• For subjects who have experienced any clinically significant toxicity related to a prior anticancer treatment (i.e., chemotherapy, immunotherapy, and/or radiotherapy): at the time the subject provides voluntary written informed consent, all toxicities have either resolved to grade 1 per NCI CTCAE Version 5.0 \[11\] OR are clinically stable and no longer clinically significant.
• Have measurable disease as defined by RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Males or females are \>18 years of age at the time of providing voluntary written informed consent.
• Life expectancy \>3 months before enrollment.
• Time between prior anticancer therapy and first dose of tazemetostat as follows:
• Cytotoxic chemotherapy - At least 21 days Noncytotoxic chemotherapy (e.g., small molecule inhibitor) - At least 14 days. Nitrosoureas - At least 6 weeks. Monoclonal antibody - At least 28 days. Radiotherapy - At least 14 days. In addition, at least 6 weeks from prior radioisotope therapy; and at least 12 weeks from 50% pelvic or total body irradiation.
• Adequate renal function: Creatinine \< 2.0 or calculated creatinine clearance ≥ 35 mL/minute per the Cockcroft and Gault formula
• Adequate bone marrow function:
• ANC ≥ 750mm3 without growth factor support (filgrastim or pegfilgrastim) for at least 14 days.
• Platelets ≥ 75,000mm3 (≥75 × 109/L) evaluated at least 7 days after platelet transfusion.
• Hemoglobin ≥9.0 g/dL and may receive transfusion Adequate liver function: Total bilirubin \<1.5 × the upper limit of normal (ULN) (except for unconjugated hyperbilirubinemia of Gilbert's syndrome); Alkaline phosphatase (ALP) (in the absence of bone disease), ALT, and AST \<3 × ULN (or \<5 × ULN if subject has liver metastases).

You may not qualify if:

• Subjects with epithelioid sarcoma are excluded.
• Has a prior history of T-Cell Lymphoblastic Lymphoma, T-Cell Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Acute Myeloid Leukemia, or Myeloproliferative Neoplasm.
• Female subjects who are pregnant or breastfeeding.
• Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
• Subjects with uncontrolled CNS metastases requiring steroids.
• Subjects taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's wort)
• Are unwilling to exclude Seville oranges, grapefruit juice, AND grapefruit from their diet.
• Major surgery within 4 weeks before the first dose of study drug. NOTE: Minor surgery (e.g., minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 1 week prior to enrollment.
• Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat.
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II (Appendix 3), uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia.
• Have an active infection requiring systemic therapy.
• Known hypersensitivity to any component of tazemetostat.
• Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.
• Subjects who have undergone a solid organ transplant.
• Prior malignancy in the past 5 years.

Sponsors & Collaborators

• Prisma Health-Upstate: lead
• Ipsen: collaborator

Study Sites (1)

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

Location

Related Publications (5)

• Xu G, Chhangawala S, Cocco E, Razavi P, Cai Y, Otto JE, Ferrando L, Selenica P, Ladewig E, Chan C, Da Cruz Paula A, Witkin M, Cheng Y, Park J, Serna-Tamayo C, Zhao H, Wu F, Sallaku M, Qu X, Zhao A, Collings CK, D'Avino AR, Jhaveri K, Koche R, Levine RL, Reis-Filho JS, Kadoch C, Scaltriti M, Leslie CS, Baselga J, Toska E. ARID1A determines luminal identity and therapeutic response in estrogen-receptor-positive breast cancer. Nat Genet. 2020 Feb;52(2):198-207. doi: 10.1038/s41588-019-0554-0. Epub 2020 Jan 13.

  PMID: 31932695 BACKGROUND

• Bitler BG, Aird KM, Garipov A, Li H, Amatangelo M, Kossenkov AV, Schultz DC, Liu Q, Shih IeM, Conejo-Garcia JR, Speicher DW, Zhang R. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Nat Med. 2015 Mar;21(3):231-8. doi: 10.1038/nm.3799. Epub 2015 Feb 16.

  PMID: 25686104 BACKGROUND

• Yamada L, Saito M, Thar Min AK, Saito K, Ashizawa M, Kase K, Nakajima S, Onozawa H, Okayama H, Endo H, Fujita S, Sakamoto W, Saze Z, Momma T, Mimura K, Ohki S, Kono K. Selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer. Gastric Cancer. 2021 Jan;24(1):60-71. doi: 10.1007/s10120-020-01094-0. Epub 2020 Jun 6.

  PMID: 32506298 BACKGROUND

• Sen M, Wang X, Hamdan FH, Rapp J, Eggert J, Kosinsky RL, Wegwitz F, Kutschat AP, Younesi FS, Gaedcke J, Grade M, Hessmann E, Papantonis A, Strӧbel P, Johnsen SA. ARID1A facilitates KRAS signaling-regulated enhancer activity in an AP1-dependent manner in colorectal cancer cells. Clin Epigenetics. 2019 Jun 19;11(1):92. doi: 10.1186/s13148-019-0690-5.

  PMID: 31217031 BACKGROUND

• Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011 May 12;117(19):5019-32. doi: 10.1182/blood-2011-01-293050. Epub 2011 Feb 7.

  PMID: 21300984 BACKGROUND

MeSH Terms

Interventions

tazemetostat

Study Officials

• Ki Chung, MD

  Prisma Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: August 26, 2021
• Study Start: January 6, 2022
• Primary Completion: March 6, 2026
• Study Completion: March 6, 2026
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: beginning 6 months following publication of study results and ending 24 months post publication
• Access Criteria: Data request must be submitted to the principal investigator, reviewed and approved by the study investigators.

Locations

US (1)