Approval Probability
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Adjusted LOA
ML Risk
Also known as voreloxin, Qinprezo, SNS-595, SNS-595 Injection
Vosaroxin · 11 trials · 14 indications
Vosaroxin + cytarabine patient survival versus placebo + cytarabine patient survival
Efficacy assessments
Combined remission rate (complete remission \[CR\] + complete remission with incomplete platelet recovery \[CRp\]) of vosaroxin of patients ≥ 60 years old with previously untreated (de novo or secondary) AML are presented by treatment group for all treated analysis set. Per IWG criteria, a CR requires bone marrow blasts \< 5%, absolute neutrophil count (ANC) \> 1000 cells/uL, and platelet (plt) count \> 100,000 plt/uL. The criteria for CRp are the same as those for CR, except for platelet count \<= 100,000 lt/uL. Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (Morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.
Objective tumor response rate based on the RECIST criteria for target lesions as assessed by CT or MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD), at least a 20% increase in the sum of the LD of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Overall Response (OR) = CR + PR
ORR is based on RECIST criteria to SNS-595 as a second-line therapy in patients with advanced NSCLC. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Maximum tolerated dose (MTD) defined as highest daily oral dose evaluated at which \<33% of patients experience a dose limiting toxicity (DLT). A non-hematologic dose-limiting toxicity (DLT) defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to CTCAE criteria) assessed by treating physician as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during the first 28 days on study. A hematologic DLT defined as severe myelosuppression with a hypoplastic marrow with less than 5% cellularity and no evidence of leukemia 42 days from start of therapy. This will define severe and delayed myelosuppression not related to persistent leukemia and likely related to treatment.
Maximum tolerated dose of vosaroxin for short IV infusion in INT-2 or high-risk MDS
Defined as the highest dose of vosaroxin that results in a DLT in =\< 1 of 6 patients graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0
| Arm | Type | Description |
|---|---|---|
| Group A: vosaroxin + cytarabine | EXPERIMENTAL | vosaroxin (short IV infusion within 10 minutes) on days 1 and 4: cytarabine on days 1 through 5; a maximum of 2 cycles of Induction and 2 cycles for Consolidation |
| Group B: placebo + cytarabine | PLACEBO_COMPARATOR | placebo (short IV infusion within 10 minutes and volume matched to vosaroxin) on days 1 and 4: cytarabine on days 1 through 5; a maximum of 2 cycles of Induction and 2 cycles for Consolidation |
| Azacitidine + Vosaroxin | OTHER | Cycle 1-8: Azacitidine: 75 mg/m²/d subcutaneously, d 1-7; Vosaroxin: Dose Level 0: 70mg/m², Dose Level -1: 50mg/m², Dose Level -2: 40mg/m², IV over ten minutes, d 1+4 . Patients who have completed 8 cycles of azacitidine and vosaroxin are scheduled to maintenance with single agent azacitidine at 75 mg/m²/d on days 1-7 until relapse or progression. |
| All Study Patients | EXPERIMENTAL | * Schedule A: 72 mg/m2 vosaroxin Days 1, 8 and 15 * Schedule B: 72 mg/m2 vosaroxin on Days 1 and 8 * Schedule C: 72 mg/m2 on Days 1 and 4, or * Schedule C: 90 mg/m2 on Days 1 and 4 |
| SNS-595 | EXPERIMENTAL | SNS-595; 48 mg/m2 administered IV once every 21 days for up to 6 cycles. |
| Treatment with 48 mg/m2 of SNS-595 | EXPERIMENTAL | Patients are treated with 48 mg/m2 of the drug SNS-595 injection once every 21 days for up to 6 cycles as a second -line therapy to patients with advanced non-small cell lung cancer (NSCLC) |
| Vosaroxin + Decitabine | EXPERIMENTAL | The first 6 patients on study (first cohort) receive 1 or 2 induction cycles of therapy according to the following starting schedule: Vosaroxin administered intravenously on days 1 and 4 at a dose of 90 mg/m2 in the first cycle (induction 1) for a total dose of 180 mg/m2/cycle in combination with Decitabine at a dose of 20 mg/m2 intravenously daily for 5 consecutive days (Days 1 to 5). Following the phase I portion, patients in phase II receive the following induction: 1. Vosaroxin intravenously on days 1 and 4 at a dose of 70 mg/m2 for a total dose of 140 mg/m2/cycle (days 1 and 4), or the final induction dose (MTD) determined in phase I. 2. Decitabine intravenously at a dose of 20 mg/m2 for 5 consecutive days (days 1 to 5), or the final induction dose (MTD) determined in phase I. |
| Vosaroxin: All Patients | EXPERIMENTAL | All patients will receive vosaroxin according to the dose cohort in which they are enrolled. |
| Treatment (vosaroxin, azacitidine) | EXPERIMENTAL | Patients receive vosaroxin IV over 10 minutes on days 1 and 4 and azacitidine SC or IV over 15 minutes on days 1-7. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. |
| Sch A (18 mg/m2 vosaroxin initially) | EXPERIMENTAL | Once weekly intravenous on days 1, 8, 15 up to 4 cycles |
| Sch B (9 mg/m2 vosaroxin initially) | EXPERIMENTAL | Twice weekly intravenous administration on days 1, 4, 8, 11 up to 4 cycles |
| Name | Type | Description |
|---|---|---|
| vosaroxin + cytarabine | DRUG | Vosaroxin days 1 and 4: 90 mg/m2 for induction 1; 70 mg/m2 for all other cycles Cytarabine 1 g/m2 daily on days 1-5 (IDAC) |
| placebo + cytarabine | DRUG | Placebo days 1 and 4: volume matched to vosaroxin Cytarabine 1 g/m2 daily on days 1-5 (IDAC) |
| Vosaroxin | DRUG | Cycle 1-8: Dose Level 0: 70mg/m², Dose Level -1: 50mg/m², Dose Level -2: 40mg/m², IV over ten minutes, d 1+4 . |
| Azacitidine | DRUG | Cycle 1-8 Azacitidine: 75 mg/m²/d subcutaneously, d 1-7; Maintenance with single agent azacitidine at 75 mg/m²/d on days 1-7 until relapse or progression. |
| SNS-595 | DRUG | - |
| SNS-595 Injection | DRUG | Vosaroxin (formerly voreloxin or SNS-595) is a first in class anticancer quinolone derivative, non anthracycline topoisomerase II inhibitor. It induces replication dependent DNA damage by intercalating DNA and inhibiting topoisomerase II, leading to apoptosis. |
| Decitabine | DRUG | Phase I and II: 20 mg/m2 by vein daily for 5 consecutive days (Days 1 to 5). |
Inclusion Criteria: * Provided signed, written informed consent * At least 18 years of age * Had a diagnosis of AML according to World Health Organization (WHO) classification * First relapsed or refractory AML (refractory to initial induction therapy) with at least 5% blasts by bone marrow or aspi...
Vosaroxin is an investigational small molecule being developed by Viracta Therapeutics, Inc. (ticker VIRX) for blood cancers. It has been studied in acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, and related leukemias. It is a Phase 3-stage asset and has not been approved by the FDA.
Vosaroxin has been studied for acute myeloid leukemia, including newly diagnosed disease in older patients, and for myelodysplastic syndrome. Trials have combined it with agents such as azacitidine and decitabine. It remains investigational and is not an approved treatment for acute myeloid leukemia.
Vosaroxin targets TOP2A and TOP2B, two topoisomerase II enzymes. It acts as an inhibitor of these targets. By inhibiting topoisomerase II, vosaroxin interferes with DNA processes in cancer cells. This mechanism underlies its investigation in acute myeloid leukemia, leukemia, and myelodysplastic syndrome.
Vosaroxin is developed by Viracta Therapeutics, Inc., which trades under the ticker VIRX. The company is the sponsor behind the clinical program evaluating vosaroxin in hematologic cancers, including acute myeloid leukemia and myelodysplastic syndrome.
Vosaroxin is in Phase 3 development. It is an investigational agent and has not been approved by the FDA. The program includes completed Phase 1 and Phase 2 trials, and the overall development stage is Phase 3.
Vosaroxin has been evaluated in completed trials including NCT03338348, which tested vosaroxin with azacitidine in newly diagnosed acute myeloid leukemia or myelodysplastic syndrome with excess blasts-2, and NCT01980056 in intermediate-2 or high-risk myelodysplastic syndrome after hypomethylating agent failure. Other completed studies include NCT01913951 and NCT01893320.