Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Osimertinib, osimertinib
AZD9291 · 11 trials · 9 indications
Defined as the time from the date of randomization until the date of disease recurrence or death (by any cause in the absence of recurrence).
As a measure of the safety and tolerability of osimertinib in combination with durvalumab the number of subjects who experienced any treatment emergent AE (TEAE), any causally related AE, any serious AE (SAE), and any causally related SAE are presented.
To assess the efficacy of various sequences. CR (per RECIST 1.1 as assessed by the local/site Investigator) is defined as the disappearance of all target and non-target lesions. Confirmed complete response rate (CR rate) is defined as the number (%) of patients with a confirmed overall response of CR and was based on the evaluable analysis set.
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (according to independent review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
Pharmacokinetics of AZD9291 after single dosing by assessment of maximum plasma AZD9291 concentration
Pharmacokinetics of AZD9291 metabolites (AZ5104) after single dosing by assessment of maximum plasma concentration
Pharmacokinetics of AZD9291 metabolites (AZ7550) after single dosing by assessment of maximum plasma concentration
Pharmacokinetics of AZD9291 after single dosing by assessment of area under the plasma concentration time curve from zero to infinity
Pharmacokinetics of AZD9291 metabolites (AZ5104) after single dosing by assessment of area under the plasma concentration time curve from zero to infinity
Pharmacokinetics of AZD9291 metabolites (AZ7550) after single dosing by assessment of area under the plasma concentration time curve from zero to infinity
Rate and extent of absorption of single dose AZD9291 by assessment of apparent clearance following oral administration
Pharmacokinetics of AZD9291 after multiple dosing by assessment of maximum plasma concentration at steady state
Pharmacokinetics of AZD9291 metabolites (AZ5104) after multiple dosing by assessment of maximum plasma concentration at steady state
Pharmacokinetics of AZD9291 metabolites (AZ7550) after multiple dosing by assessment of maximum plasma concentration at steady state
Pharmacokinetics of AZD9291 after multiple dosing by assessment of area under the plasma concentration curve from time zero to the end of the dosing interval
Pharmacokinetics of AZD9291 metabolites (AZ5104) after multiple dosing by assessment of area under the plasma concentration curve from time zero to the end of the dosing interval
Pharmacokinetics of AZD9291 metabolites (AZ7550) after multiple dosing by assessment of area under the plasma concentration curve from time zero to the end of the dosing interval
Pharmacokinetics of AZD9291 after multiple dosing by assessment of apparent plasma clearance at steady state
Absolute bioavailability of AZD9291 will be calculated from area under the plasma concentration versus time curve (AUC) of the oral dose of AZD9291 / AUC of the IV dose of \[14C\]AZD9291 x IV dose/Oral dose x 100
Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 72 hours.
Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration.
Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to infinity
The percentage of radioactive dose of \[14C\] radiolabelled AZD9291 recovered in urine, faeces, and in total, up to Day 85.
Curve taken during each of the 5 treatments
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (by investigator assessment) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. Not evaluable (NE): TL response is missing and there is no evidence of progression of NTLs and no new lesions. BOR is the best response (by investigator assessment) a patient has achieved where the order of best to worst is CR, PR, SD, PD, NE prior to or at progression and prior to further anti-cancer therapy.
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (by independent central review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
| Arm | Type | Description |
|---|---|---|
| AZD9291 | EXPERIMENTAL | AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule. |
| Placebo AZD9291 | PLACEBO_COMPARATOR | Matching placebo for AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule. |
| MEDI4736 & AZD9291 Combination | EXPERIMENTAL | 10mg/kg q2w (IV) infusion \& once daily tablet 80 mg |
| AZD9291 Monotherapy | EXPERIMENTAL | Once daily tablet 80 mg |
| Gefitinib with a Seq. Switch to a MEDI4736 | EXPERIMENTAL | Gefitinib once daily followed by MEDI4736 |
| AZD9291 with a Seq. Switch to a MEDI4736 | EXPERIMENTAL | AZD9291 once daily followed by MEDI4736 |
| Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736 | EXPERIMENTAL | Selumetinib twice daily + docetaxel, followed by MEDI4736 |
| Tremelimumab with a Seq. Switch to a MEDI4736 | EXPERIMENTAL | Tremelimumab every 4 weeks followed by MEDI4736 |
| AZD9291 40 mg | EXPERIMENTAL | Cohort 1: 40 mg once daily |
| AZD9291 80 mg | EXPERIMENTAL | Cohort 2: 80 mg once daily |
| Bioavailability of AZD9291 | EXPERIMENTAL | To assess the absolute bioavailability of a single oral dose of AZD9291 with respect to an intravenous microdose of \[14C\]AZD9291 |
| Fasted | OTHER | AZD9291 tablets following a period of fasting |
| High-fat meal | OTHER | AZD9291 tablets following a high-fat meal. |
| AZD9291 alone, AZD9291+itraconozole | EXPERIMENTAL | Sequential treatments of AZD9291 alone followed by AZD9291+itraconazole, with a washout period in between. |
| [14C]-AZD9291 20mg (oral solution) | EXPERIMENTAL | Volunteers will receive 20 mg \[14C\]-AZD9291 containing a nominal 1 μCi activity, administered by mouth, as a solution. |
| AZD9291 20mg (oral capsule fasted) | EXPERIMENTAL | Volunteers will receive AZD9291 20mg administered by mouth, as a capsule, in the fasted state. |
| AZD9291 20mg (oral solution fasted) | EXPERIMENTAL | Volunteers will receive AZD9291 20mg administered by mouth, as a solution, in the fasted state. |
| AZD9291 20mg (oral tablet fasted) | EXPERIMENTAL | Volunteers will receive AZD9291 20mg administered by mouth, as a tablet, in the fasted state. |
| AZD9291 20mg (oral fasted) | EXPERIMENTAL | Volunteers will receive AZD9291 20mg administered by mouth, as a capsule or tablet in the fasted state. |
| AZD9291 20mg (oral fed) | EXPERIMENTAL | Volunteers will receive AZD9291 20mg administered by mouth, as a capsule or tablet in the fed state. |
| Daily dose of AZD9291 | EXPERIMENTAL | Daily oral dose of AZD9291 |
| Name | Type | Description |
|---|---|---|
| AZD9291 80 mg/40 mg | DRUG | The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily. |
| Placebo AZD9291 80 mg/40 mg | DRUG | The initial dose of Placebo AZD9291 80 mg once daily can be reduced to 40 mg once daily. |
| Open-label AZD9291 80 mg/40 mg | DRUG | Eligible patients will be offered open-label osimertinib upon recurrence and in the absence of intervening systemic anti-cancer therapy. |
| AZD9291 | DRUG | Once daily tablet 80 mg |
| MEDI4736 | DRUG | 10mg/kg q2w (IV) infusion |
| Gefitinib | DRUG | Gefitinib once daily followed by MEDI4736 |
| Selumetinib+Docetaxel | DRUG | Selumetinib twice daily + docetaxel, followed by MEDI4736 |
| Tremelimumab | DRUG | Tremelimumab every 4 weeks followed by MEDI4736 |
| AZD9291 40 mg | DRUG | This is a two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg Cohort 1 and 80 mg Cohort 2) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). |
| AZD9291 80 mg | DRUG | This is a two parts (Part A and Part B) study to determine the pharmacokinetics of AZD9291 administered orally at two dose levels (40 mg Cohort 1 and 80 mg Cohort 2) in patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). |
| [14C]AZD9291 | DRUG | Each healthy male subject will also receive a single, radiolabeled, 100 μg dose of \[14C\] AZD9291 administered as an IV microdose infusion starting at 5 hours and 45 minutes after receiving the oral dose. |
| AZD9291 tablets | DRUG | AZD9291 tablets: Part A 80mg od, days 1 and 10 only. Part B 80mg od for 12 months. |
| Pharmacokinetic sampling - AZD9291 | PROCEDURE | Blood samples taken pre and post dosing of AZD9291 following either a period of fasting or consumption of a meal. |
| Dietary Fasted | OTHER | Fasted from 10 hours prior to dosing with 80mg AZD9291 tablet and 4 hours after dosing |
| Dietary High Fat | OTHER | Allocated breakfast prior to dosing with 80mg AZD9291 tablet |
| Pharmacokinetic sampling - AZ5140 and AZ7550 | PROCEDURE | Blood samples taken pre and post dosing of AZD9291 following either a period of fasting or consumption of a meal. |
| Pharmacokinetic sampling | PROCEDURE | Blood samples taken pre and post dosing with AZD9291+/- itraconazole |
| Itraconazole | DRUG | Itraconazole tablets: 2x100mg bd, Part A days 6 to 19 only |
Inclusion Criteria: 1. Male or female, aged at least 18 years. 2. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on predominantly non-squamous histology 3. MRI or CT scan of the brain must be done prior to surgery as it is considered standard of care. 4. Patients must b...
AZD9291, also known as osimertinib, is an investigational small molecule being studied for the treatment of locally advanced or metastatic EGFR T790M+ non-small cell lung cancer (NSCLC), as well as other stages of NSCLC including stage II-IIIB and stage IV disease. It is being evaluated in patients with EGFR mutation positive locally advanced or metastatic NSCLC.
AZD9291 is a kinase inhibitor, belonging to the -tinib class of drugs. It targets and inhibits kinase enzymes involved in cancer cell growth and survival. Specifically, it is being studied in EGFR T790M mutation positive NSCLC, indicating its activity against the EGFR kinase with the T790M resistance mutation.
AZD9291 is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker symbol AZN. The drug is also known by its generic name osimertinib and is currently in clinical development for the treatment of non-small cell lung cancer.
AZD9291 is in Phase 1 clinical development, with a total of 9 trials, of which 7 are active and 3 are completed. The trials include Phase 1, Phase 2, and Phase 3 studies, with a total enrollment of 2420 participants. The drug has received FDA priority review designation.
AZD9291 is being studied in several clinical trials, including NCT02491944, a completed Phase 1 bioavailability study; NCT02856893, a completed Phase 2 study in EGFR T790M plasma positive NSCLC patients; NCT03521154, an active Phase 3 study in stage III unresectable NSCLC; and NCT05526755, an active Phase 2 study of adjuvant therapy in resected EGFRm NSCLC.
Yes, AZD9291 is the same as osimertinib. The drug is known by multiple names, including osimertinib, Osimertinib 80 mg/40 mg, and Osimertinib + Savolitinib. These names refer to the same investigational drug being developed by AstraZeneca for the treatment of EGFR mutation positive non-small cell lung cancer.