Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Azacitidine
APR-246 · 7 trials · 13 indications
To compare the complete response rate, defined as the proportion of patients who achieve complete remission (CR) with APR 246 + azacitidine treatment vs. azacitidine only.
Relapse-free survival (RFS) at 12 months or longer if data permits. RFS was defined as the time from HCT to relapse after HCT or death, whichever occurred first.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.
To determine the Frequency of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) related to APR-246 in combination with pembrolizumab.
To determine the dose of APR-246 to be selected for the expansion phase based on the occurence of dose limiting toxicities (DLTs) experienced during the safety assessment period
1\. Dose-limiting toxicities (DLTs), classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0).
DLT: Hematological and non-hematological toxicities according to grade/days stated in the protocol.
Phase Ib: Progression-free Survival is calculated from date of enrollment to the date of disease progression or death due to any cause, whichever occurs first. Symptomatic deterioration is not considered PD. For a patient without evidence of disease progression or death, Progression-free survival will be censored at the date of last evaluable tumor assessment. Patients with no evaluable tumor assessments will be censored at the date of first study drug administration. Phase II: Progression-free survival (PFS) based on Blinded Independent Central Review (BICR) is the primary endpoint and is defined as the number of days from the date of randomization to the date of objective disease progression or relapse (according to RECIST v1.1 only) or death due to any cause, whichever occurs first. If neither event occurs, PFS is censored at the date of the last evaluable tumor assessment. Symptomatic deterioration is not considered objective disease progression.
| Arm | Type | Description |
|---|---|---|
| Experimental arm: APR-246 + azacitidine | EXPERIMENTAL | Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65): |
| Control arm: Azacitidine | EXPERIMENTAL | Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65): |
| APR-246 + PLD | EXPERIMENTAL | - |
| Safety Lead In-Phase 1 Dose Level 1 | EXPERIMENTAL | APR-246 4.5g/d with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced non-CNS primary tumors |
| Expansion 1- Gastric Cancer | EXPERIMENTAL | APR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced gastric or GEJ tumors |
| Expansion 2- Bladder Cancer | EXPERIMENTAL | APR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced bladder or urothelial tumors |
| Expansion 3 -NSCLC | EXPERIMENTAL | APR-246 4.5 g/d (days 1-4) with pembrolizumab 200 mg IV (day 3) every 21 days in patients with advanced NSCLC. |
| APR-246 | EXPERIMENTAL | APR-246 4.5 g/day |
| Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD. | EXPERIMENTAL | Dose escalation of APR-246. |
| Phase II: Arm A. APR-246 + Carboplatin/PLD. | EXPERIMENTAL | Experimental |
| Phase II: Arm B. Carboplatin/PLD. | ACTIVE_COMPARATOR | Active Comparator |
| Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD. | EXPERIMENTAL | Dose escalation of APR-246. |
| Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD. | EXPERIMENTAL | Dose escalation of APR-246. |
| Name | Type | Description |
|---|---|---|
| APR-246 + azacitidine | DRUG | Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65): Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine |
| Azacitidine | DRUG | Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65): Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine |
| APR-246 | DRUG | APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles. |
| Pegylated Liposomal Doxorubicin Hydrochloride (PLD) | DRUG | Intravenous infusion |
| APR-246 (eprenetapopt) + Pembrolizumab | DRUG | APR-246 D1-4 + Pembrolizumab D3 |
| Venetoclax | DRUG | Venetoclax 400 mg once daily |
| Carboplatin and Pegylated Liposomal Doxorubicin Hydrochloride (PLD) | DRUG | Intravenous infusion. |
Inclusion Criteria: * Signed Informed Consent (ICF) and is able to comply with protocol requirements * Documented diagnosis of MDS, according to World Health Organization (WHO) classification * Patient has adequate organ function as defined by the following laboratory values: 1. Creatinine clear...
APR-246 is an investigational small molecule studied in TP53-mutant cancers, including acute myeloid leukemia, myelodysplastic syndromes, and myeloid malignancies. It has also been evaluated in solid tumors such as bladder cancer, urothelial carcinoma, gastric cancer, and non-small cell lung cancer. It is being developed by Aprea Therapeutics and is not approved for commercial use.
APR-246 targets p53, a tumor suppressor protein. The drug is designed to act on mutant p53, which is frequently altered in myeloid malignancies and other cancers. Studies of APR-246 have focused on biomarker-selected patients whose tumors carry TP53 mutations, including trials combining it with azacitidine, venetoclax, or pembrolizumab.
APR-246 is developed by Aprea Therapeutics, Inc., which trades under the ticker APRE. The company has sponsored clinical studies of APR-246 both as a single agent and in combination regimens, including pairings with azacitidine, venetoclax, and pembrolizumab, across hematologic and solid tumor indications.
APR-246 is in Phase 2 development overall and remains investigational. Its clinical program has included a completed Phase 3 study in TP53-mutant myelodysplastic syndromes, along with completed Phase 1 and Phase 2 trials in myeloid malignancies and solid tumors. No regulatory approval of APR-246 has been established.
Completed APR-246 trials include NCT03931291, a Phase 2 study with azacitidine after allogeneic stem cell transplant in TP53-mutated AML or MDS; NCT03745716, a Phase 3 study with azacitidine in TP53-mutant MDS; NCT04214860, a Phase 1 study with venetoclax and azacitidine in myeloid malignancies; and NCT04383938, a Phase 1/2 study with pembrolizumab in solid tumors.
Yes. APR-246 is also known as eprenetapopt. The compound has been studied under both names, including in combination regimens such as APR-246 plus azacitidine and APR-246 plus pembrolizumab. Searches for eprenetapopt, APR-246, or those combination names refer to the same p53-targeting agent from Aprea Therapeutics.