Tuvusertib in Astrocytoma With ATRX Mutation

NCT07417761 | Recruiting Phase 2 DMC

• 2 other identifiers: GEINO-24012025-521843-19-00
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 10

Brief Summary

The TUVASTRAT study is a phase 2, non-randomized, two.cohort, CRS clinical trial of tuvusertib in patients with first recurrence of IDH1/2-mutated, ATRX-mutated and p53-mutated astrocytoma (Grade 2-4 from WHO classification). The mutational status of IDH (required for diagnosis) is also required. CDKN2A and ATRX will be also determined locally as per standard of care. All enrolled patients should have received first-line chemotherapy and have reported a contrast enhanced PD. Eligible patients are enrolled in two cohorts depending on their eligibility to undergo rescue surgery:

• Cohort A: First recurrence of IDH1/2-mutated, ATRX-mutated astrocytoma NOT eligible for rescue surgery.
• Cohort B: First recurrence of IDH1/2-mutated, ATRX-mutated astrocytoma candidates to rescue surgery. The primary hypothesis is that treatment with tuvusertib, an ATR inhibitor, will improve the efficacy outcomes and increase the 6-months PFS rate from 45% reported by the standard therapies up to 65% in patients with recurrent IDH-mutated astrocytomas with ATRX mutation. Clinic visits will occur every 3 weeks ±3 days. Tumor assessments by MRI according to RANO 2.0 criteria will be performed at baseline, and every 12 weeks +/-2 weeks (Q12W) until PD, patient withdrawal, start of new treatment line or death. This schedule must be maintained regardless of any delays in dosing. After the first suspect of progression, we recommend a second MRI at 4-8 weeks to confirm the progression, except if there is clinical progression. The MRI imaging will be assessed by PI and central radiologists. The trial includes the assessment of safety (AEs, comorbidities) throughout the study period at every visit, the collection of health-related patient reported outcomes through validated questionnaires at baseline, coincident with the tumor assessments and at the safety visit. Neurologic / neurocognitive status will be assessed through validated tests administered by the physicians. Additionally, ATRX, IDH, P53 and CDK2A mutations will be centrally reviewed in tumor biopsies or archival tumor tissue obtained as close as possible to the baseline. PKs will be determined in sparse peripheral blood samples during the treatment phase. The study includes a data safety monitoring committee (DSMC) to regularly review safety and efficacy. The DSMC will review efficacy and safety at least yearly and more frequently if deemed necessary.

Conditions

Astrocytoma

Keywords

Tuvusertib; Astrocytoma; IDH mutated; ATRX mutated

Outcome Measures

Primary Outcomes (1)

• 6-months progression-free survival (PFS) rate

  defined as the proportion of patients alive and free of progression according to RANO 2.0 estimated by Kaplan-Meier.

  At 6 months after the first dose of tuvusertib

Secondary Outcomes (12)

• Objective response (ORR)

  Throughout the study period, approximately an average of 2 year

• Progression-free survival (PFS)

  Throughout the study period, approximately an average of 2 year

• Overall survival (OS)

  Throughout the study period, approximately an average of 2 year

• Time to Next Intervention (TTNI)

  Throughout the study period, approximately an average of 2 year

• Neurocognitive function changes by Hopkins Verbal Learning Test-Revised (HVLT-R)

  Throughout the study period, approximately an average of 2 year

Other Outcomes (1)

• Pathologic response

  Surgery will be performed after two tuvusertib cycles (each cycle is 3 weeks), approximately within 2-3 months from first dose of study treatment

Study Arms (1)

Tuvusertib treatment

EXPERIMENTAL

TUVASTRAT is a study including patients with first recurrence of IDH1/2-mutated, ATRX-mutated and p53-mutated astrocytoma (Grade 2-4 from world health organization \[WHO\] classification). All enrolled patients should have received first-line chemotherapy as per standard clinical practice and have evidence of tumor progression with contrast enhancement. Patients included will be of the following two subgroups: Cohort A: First recurrence of IDH1/2-mutated, ATRX-mutated astrocytoma NOT eligible for rescue surgery. Cohort B: First recurrence of IDH1/2-mutated, ATRX-mutated astrocytoma candidates to rescue surgery.

Drug: Tuvusertib

Interventions

Tuvusertib DRUG

All patients will receive tuvusertib at the recommended dose (for) expansion (RDE) of 180 mg daily (QD) during 2 weeks on and 1 week off.

Tuvusertib treatment

Eligibility Criteria

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

You may qualify if:

• Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities.
• Patients, males and females, ≥ 18 years of age at the time of signing the informed consent.
• Patients with Karnofsky performance status (KPS) index \> 60% (Appendix 5).
• Diagnosis of Grade 2-4 astrocytoma, IDH-mutated according to the 2021 WHO classification.
• Patients must have confirmed ATRX mutation (IHC or NGS sequencing) and p53 mutation (NGS sequencing). Evaluation of CDKN2A also is required by FISH or NGS.
• Patients must have progressive disease and evaluable disease according to RANO 2.0 criteria. All patients should have MRI contrast enhancement disease.
• Patients must have undergone previous standard treatment with radiotherapy and chemotherapy (procarbazine, lomustine and vincristine \[PCV\] or temozolomide \[TMZ\]).
• Stable corticosteroid doses during the 2 weeks previous to the first dose of tuvusertib, maximum dose of dexamethasone 4 mg/day or equivalent.
• Adequate hematologic, hepatic and renal function as follows:
• Platelet count ≥ 100,000/mm3,
• Hemoglobin ≥ 9.0 g/dL,
• Absolute neutrophil count ≥ 1,500/μL with no growth factor treatment within the last 14 days,
• Total bilirubin level ≤ 1.5 × upper limit of normal (ULN) (if Gilbert's Syndrome may have total bilirubin \> 1.5 × ULN),
• Aspartate aminotransferase (AST) level ≤ 3 × ULN, and an alanine aminotransferase (ALT) level ≤ 3 × ULN.
• Serum creatinine ≤ 1.5 × ULN. If serum creatinine is \> 1.5 × ULN, creatinine clearance needs to be ≥ 50 mL/min, as estimated by Cockcroft-Gault

You may not qualify if:

• Patients with radiographic recurrence without contrast enhancement by MRI.
• Leptomeningeal dissemination and/or extracranial metastases.
• Patients who received more than 1 previous systemic line of treatment for astrocytoma.
• Patients who received previous treatment with bevacizumab.
• Persistence of AEs related to any prior treatments that have not recovered to Grade ≤ 1 unless AEs are clinically nonsignificant (e.g. alopecia) and/or stable on supportive therapy in the opinion of the Investigator.
• No prior ATR inhibitor and/or CHK1 inhibitor.
• Concurrent treatment with a non permitted drug/intervention:
• Prohibited concomitant medication, as listed in Section 7.8.
• Anticancer treatment within 30 days or 5 half-lives, whichever is shorter, prior to Day 1 of study intervention (6 weeks for nitrosoureas or mitomycin C).
• Prior palliative radiotherapy to metastatic lesion(s) is permitted provided it was completed ≥ 12 weeks prior to study intervention administration and participants have recovered from all related radiotherapy toxicities to Grade ≤ 1.
• Another investigational drug within 30 days or 5 half-lives, whichever is shorter, prior to start of tuvusertib administration.
• Increasing dose of corticoids.
• Received hematopoietic growth factor (e.g., granulocyte colony-stimulating factor, erythropoietin) within 14 days prior to the first dose of tuvusertib.
• Significant cardiac disease:
• Unstable angina, myocardial infarction, congestive heart failure ≥ stage II) or a coronary revascularization procedure within 180 days of study entry.

Sponsors & Collaborators

• Grupo Español de Investigación en Neurooncología: lead

Study Sites (10)

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

Hospital Universitario de Cruces

Barakaldo, Bizkaia, 48903, Spain

RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, Granada, 18014, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

Hospital Álvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

RECRUITING

Hospital Clínico Universitario de Salamanca

Salamanca, Salamanca, 37007, Spain

NOT YET RECRUITING

Hospital Universitario Virgen del Rocío

Seville, Sevilla, 41013, Spain

RECRUITING

Hospital Clínico Universitario de Valencia - INCLIVA

Valencia, Valencia, 46010, Spain

RECRUITING

MeSH Terms

Conditions

Astrocytoma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Estela Pineda, M.D.; Ph.D.

  Medical Oncology, Hospital Clínic de Barcelona

  STUDY CHAIR

• Maria Vieito, M.D.; Ph.D.

  Medical Oncology, Hospital Universitari Vall d'Hebrón

  STUDY CHAIR

Central Study Contacts

GEINO Secretary

CONTACT

0034934344412; secretaria@geino.es

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: January 2, 2026
• First Posted: February 18, 2026
• Study Start: December 19, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-02

Locations

ES (10)