OncoMatch/Clinical Trials/NCT07417761
Tuvusertib in Astrocytoma With ATRX Mutation
Is NCT07417761 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies Tuvusertib for astrocytoma.
Treatment: Tuvusertib — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Glioblastoma
Biomarker criteria
Required: IDH1 mutation
IDH-mutated according to the 2021 WHO classification.
Required: ATRX mutation
Patients must have confirmed ATRX mutation (IHC or NGS sequencing)
Required: TP53 mutation
p53 mutation (NGS sequencing)
Required: CDKN2A any tested
Evaluation of CDKN2A also is required by FISH or NGS.
Disease stage
Required: Stage GRADE 2, GRADE 3, GRADE 4 (2021 WHO classification)
Diagnosis of Grade 2-4 astrocytoma, IDH-mutated according to the 2021 WHO classification.
Performance status
KARNOFSKY 61–100
Karnofsky performance status (KPS) index > 60%
Prior therapy
Must have received: radiation therapy
Patients must have undergone previous standard treatment with radiotherapy
Must have received: chemotherapy (procarbazine, lomustine, vincristine, temozolomide)
Patients must have undergone previous standard treatment with...procarbazine, lomustine and vincristine [PCV] or temozolomide [TMZ]
Cannot have received: bevacizumab (bevacizumab)
Patients who received previous treatment with bevacizumab.
Cannot have received: ATR inhibitor
No prior ATR inhibitor
Cannot have received: CHK1 inhibitor
No prior...CHK1 inhibitor
Lab requirements
Blood counts
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
Kidney function
Serum creatinine ≤ 1.5 × ULN. If serum creatinine is > 1.5 × ULN, creatinine clearance ≥ 50 mL/min (Cockcroft-Gault)
Liver function
Total bilirubin ≤ 1.5 × ULN (if Gilbert's Syndrome may have total bilirubin > 1.5 × ULN); AST ≤ 3 × ULN; ALT ≤ 3 × ULN
Cardiac function
QTc average (Fridericia) ≤ 450 msec for males and ≤ 470 msec for females; no unstable angina, MI, CHF ≥ stage II, or coronary revascularization within 180 days; no uncontrolled hypertension
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 ≤ 1.5 × ULN (if Gilbert's Syndrome may have total bilirubin > 1.5 × ULN), AST ≤ 3 × ULN, ALT ≤ 3 × ULN, Serum creatinine ≤ 1.5 × ULN. If serum creatinine is > 1.5 × ULN, creatinine clearance ≥ 50 mL/min, as estimated by Cockcroft-Gault
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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