Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as PB-8237, MLN8237
Alisertib · 4 trials · 7 indications
Treatment emergent adverse events are those events reported on or after the first dose of investigational product and up to 28 days after the last dose.
Objective response rate is defined as the percentage of participants demonstrating a confirmed objective response during the study.
Duration of response is measured from the time at which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented.
Disease control rate is the proportion of participants who achieve overall tumor response (confirmed CR or PR) or Stable Disease (SD) lasting for at least 24 weeks from randomization.
Progression Free Survival (PFS) is measured in months and based on the local tumor assessment. The time interval from the date of randomization until the first date on which recurrence, progression, or death due to any cause, is documented.
Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier.
Treatment emergent adverse events are those events reported on or after the first dose of investigational product and up to 28 days after last dose.
Objective response rate is defined as the percentage of participants demonstrating a confirmed objective response during the study
Duration of response is measured from the time at which measurement criteria are first met for CR or PR (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented.
Disease control rate is the proportion of patients who achieve overall tumor response (confirmed CR or PR) or SD lasting for at least 8 weeks from first dose of investigational product.
Progression Free Survival (PFS) is measured in months and based on the local tumor assessment. The time interval from the date of first dose until the first date on which recurrence, progression, or death due to any cause, is documented.
Overall survival (OS) is defined as the time from date of first dose to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier.
The MTD is the highest dose at which no more than one instance of a dose-limiting toxicity is observed among the 6 participants treated.
Less than or at least 1 out of 6 at highest dose level below the maximal administered dose. If 0 of these 3 additional participants experience a dose limiting toxicity (DLT) (1 of 6), proceed to the next dose level. If 1 or more of the 3 additional participants experience DLT (2 of 6), then dose escalation is stopped, and this dose is declared the maximal administered dose (highest dose administered). Three (3) additional participants will be entered at the next lowest dose level if only 3 participants were treated previously at that dose.
The proportion of participants experiencing an adverse event classified as an SAE will be reported by grade and type according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5, with exact 95% confidence intervals
| Arm | Type | Description |
|---|---|---|
| Cohort 1: Alisertib 30 mg BID + Paclitaxel | EXPERIMENTAL | Approximately ten participants will be enrolled in the cohort. Alisertib dose may be increased by 10 mg BID in the next cohort if 3 or fewer participants experience an Event during Cycle 1. |
| Cohort 2: Alisertib 40 mg BID + Paclitaxel | EXPERIMENTAL | Approximately ten participants will be enrolled in the cohort. Alisertib dose may be increased by 10 mg BID in the next cohort if 3 or fewer participants experience an Event during Cycle 1. |
| Cohort 3: Alisertib 50 mg BID + Paclitaxel | EXPERIMENTAL | Approximately ten participants will be enrolled in the cohort. Alisertib dose may be increased by 10 mg BID in the next cohort if 3 or fewer participants experience an Event during Cycle 1. |
| Cohort 4: Alisertib 60 mg BID + Paclitaxel | EXPERIMENTAL | Approximately ten participants will be enrolled in the cohort. Alisertib dose may be increased by 10 mg BID in the next cohort if 3 or fewer participants experience an Event during Cycle 1. |
| Cohort 5: Alisertib 70 mg BID + Paclitaxel | EXPERIMENTAL | Approximately ten participants will be enrolled in the cohort. |
| Alisertib 50 mg | EXPERIMENTAL | Alisertib with selected endocrine therapy |
| Alisertib 40 mg | EXPERIMENTAL | Alisertib with selected endocrine therapy |
| Alisertib 30 mg | EXPERIMENTAL | Alisertib with selected endocrine therapy Cohort closed to enrollment in Amendment 4 |
| Alisertib | EXPERIMENTAL | 50 mg (Prior to Amendment 2) or 60 mg (Amendment 2) or 70 mg (Amendment 3 or later) of alisertib PO BID on days 1-7 of each 21-day cycle |
| Dose Escalation (Closed to Enrollment) | EXPERIMENTAL | Patients will continue to receive osimertinib 80 mg PO daily as part of standard of care therapy during screening and study treatments. Alisertib will be administered to eligible patients in combination with osimertinib at doses ranging from 20 mg to 50 mg PO twice daily on days 1-3, 8-10, and 15-17 of a 28-day cycle. The starting alisertib dose will be 30 mg twice daily (dose level 1). All patients at a given dose level must complete the DLT period before any additional cohorts can be opened. |
| Dose Expansion: Cohort A | EXPERIMENTAL | Stage IV EGFR-mutant NSCLC currently receiving and progressing on osimertinib who have received no more than one additional line of systemic cancer therapy other than osimertinib (e.g., chemotherapy +/- immunotherapy, amivantamab +/- Lazertinib) for metastatic disease. Patients may receive alisertib therapy until lack of clinical benefit or intolerable toxicity. |
| Dose Expansion: Cohort B | EXPERIMENTAL | Stage IV EGFR-mutant NSCLC patients who are currently receiving first line osimertinib treatment and have received at least 3 months, but no more than 6 months, of osimertinib with a best response of PR or SD. Patients may receive alisertib therapy until lack of clinical benefit or intolerable toxicity. |
| Dose Expansion: Cohort C | EXPERIMENTAL | Stage IV EGFR-mutant NSCLC patients with no known tumor non-synonymous TP53 genomic alteration who are currently receiving first line osimertinib treatment and have received at least 3 months, but no more than 6 months, of osimertinib with a best response of PR or SD. Patients may receive alisertib therapy until lack of clinical benefit or intolerable toxicity. |
| Name | Type | Description |
|---|---|---|
| Alisertib | DRUG | Alisertib enteric-coated tablets, 30 mg BID self-administered orally on Days 1-7 of every 21-day cycle |
| Paclitaxel | DRUG | 60 mg/m\^2 IV on Days 1 and 8 of every 21-day cycle |
| Endocrine therapy | DRUG | Investigator selected endocrine therapy will be taken in 28-day dosing cycles according to the approved prescribing information. 1 mg of anastrozole tablet by mouth once daily or 2.5 mg of letrozole tablet by mouth once daily or 25 mg of exemestane tablet by mouth once daily or 20 mg of tamoxifen tablet by mouth once daily or 500 mg of fulvestrant intramuscular injection on Study Day 1, 15, 29, and once every 28 days thereafter |
| Osimertinib | DRUG | Osimertinib is a medication used to treat non-small-cell lung carcinomas with a specific mutation. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor. Patients will be receiving full dose osimertinib (80 mg PO daily) as part of the patient's current standard of care. |
Inclusion Criteria: * Aged ≥18 years at signing of informed consent * Pathologically confirmed SCLC * Prior treatment with one platinum-based chemotherapy and an anti-PD-1/PD-L1 immunotherapy. Up to one additional systemic anti-cancer therapy for SCLC is allowed, for a total of up to 2 prior treatm...
Alisertib is an investigational oral therapy being studied in several cancer types, including hormone receptor positive, HER2 negative breast cancer, small cell lung cancer, and metastatic EGFR-mutant lung cancer. It is not approved for any indication and remains in clinical development under Puma Biotechnology.
Alisertib targets AURKA, also known as Aurora kinase A. It acts as an inhibitor of this enzyme, which regulates cell division. By blocking AURKA, alisertib is designed to disrupt mitotic progression in cancer cells. This mechanism underlies its study across multiple solid tumor types.
Alisertib is being developed by Puma Biotechnology Inc, which trades on the Nasdaq under the ticker PBYI. The company is sponsoring Phase 2 studies of the drug in breast cancer and small cell lung cancer, as well as a Phase 1 combination study in metastatic lung cancer.
Alisertib is in Phase 2 clinical development. Puma Biotechnology is running Phase 2 trials in HR-positive, HER2-negative breast cancer and small cell lung cancer, plus a Phase 1 trial in metastatic EGFR-mutant lung cancer. The drug is investigational and has not been approved by the FDA.
Alisertib is being evaluated in four recruiting studies: NCT07465757 with paclitaxel in small cell lung cancer, NCT06369285 with endocrine therapy in HR-positive, HER2-negative breast cancer, NCT06095505 in extensive stage small cell lung cancer, and NCT04085315 with osimertinib in metastatic EGFR-mutant lung cancer.
Yes, alisertib trials include biomarker-selected patient populations. The Phase 1 study NCT04085315 enrolls patients with EGFR-mutant metastatic lung cancer, and the breast cancer study NCT06369285 focuses on hormone receptor positive, HER2 negative disease, reflecting a targeted development approach.