Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication TAGRISSO is a kinase inhibitor indicated for: • adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. FDA label
Also known as AZD9291, Osimertinib (AZD9291) pemetrexed cisplatin or carboplatin, Osimertinib pemetrexed cisplatin or carboplatin, AZD9291 tablets, Osimertinib First-Line, Osimertinib Third-Line, TAGRISSO, Platinum-based Doublet-Chemotherapy
Osimertinib · 31 trials · 19 indications
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression).
Safety and tolerability of osimertinib will be assessed.
DFS is defined as the time from the date of randomisation until the date of disease recurrence or date of death (by any cause in the absence of recurrence), whichever occurs first. Stratification to the high risk stratum will be based on pathologic features assessed by central pathology review during screening.
Progression free survival is defined as time from randomization until progression (intracranial or extracranial, whichever occurs first) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (for extracranial progression) and Central nervous system (CNS) RECIST 1.1 (for intracranial progression) as assessed by the Investigator at local site or death due to any cause.
Defined as ≤10% viable cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery (IASLC method). Patients will only be considered to have an MPR if they also have an R0 margin result.
Defined as ≤10% viable cancer cells in the surgical specimen, as assessed per central pathology laboratory post-surgery (chemotherapy method). Patients will only be considered to have an MPR if they also have an R0 margin result.
Adverse events were summarized by maximum reported Common Terminology Criteria for Adverse Event (CTCAE) grade, version 5.0. Grade 1 (Mild): asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate): minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 (Severe or medically significant but not immediately life-threatening): hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4 (Life-threatening consequences): urgent intervention indicated. Grade 5: Death related to AE. Includes adverse events with onset date on or after the date of first dose and up to and including 28 days following discontinuation of treatment but prior to the start of a new anti-cancer therapy.
Progression-free survival (PFS) using Investigator assessment as defined by RECIST 1.1. Median progression free survival (months) calculated using the Kaplan-Meier method. Progression-free survival (PFS) is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST assessment. The primary efficacy analysis of the investigator-assessed progression-free survival will be performed when approximately 278 PFS events and at least 16 months of follow-up after Last subject in, has occurred in the 556 randomized patients.
Sensitivity analysis for progression-free survival (PFS) by blinded independent central review (BICR) using Investigator assessment as defined by RECIST 1.1. Median progression free survival (months) calculated using the Kaplan-Meier method. Progression-free survival (PFS) is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST assessment. The primary efficacy analysis of the investigator-assessed progression-free survival will be performed when approximately 278 PFS events and at least 16 months of follow-up after Last subject in, has occurred in the 556 randomized patients.
Time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on BICR assessment according to RECIST v1.1
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.
Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS. The primary endpoint of PFS was based on Investigator assessment.
Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS.
PFS is defined as the time from date of first dose until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause.
To assess the safety and tolerability of osimertinib plus amivantamab in participants with EGFR mutation-positive, locally advanced, or metastatic NSCLC.
Defined as time from date of first dose until disease recurrence, or death due to any cause in the absence of recurrence.
DFS is defined as the time from the first dosing of study treatment until the date of disease recurrence by investigator assessment or death by any cause in the absence of disease recurrence. DFS rate at 3 years is defined as the proportion of patients alive and disease free at 3 years from the first dosing of study treatment as estimated by Kaplan-Meier method, respectively. Patients who are disease-free and alive at the time of analysis will be censored at the date of their latest follow-up assessment known to be disease-free
Objective Response Rate will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Objective Response Rate is the percent of subjects with measurable disease with at least one visit response of complete response or partial response.
Percentage of evaluable patients with an Investigator-assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target and non-target lesions and no new lesions. PR defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesions. Overall Response (OR) = CR + PR.
Absence of progressive brain metastases according to the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM criteria)
Percentage of subjects with a confirmed Objective Response (OR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). OR includes Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in target lesion diameters). OR must be recorded at one visit and confirmed by repeat imaging at least 4 weeks later, with no disease progression between initial and confirmation visits.
Percentage of subjects with a confirmed Objective Response (OR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). OR includes Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: ≥30% decrease in target lesion diameters). OR must be recorded at one visit and confirmed by repeat imaging at least 4 weeks later, with no disease progression between initial and confirmation visits.
The frequency of genetic and proteomic markers at disease progression regardless of their prevalence was evaluated.
The primary endpoint is defined as the proportion of patients at 18 months who are alive and did not experience an event for PFS by RECIST 1.1 while receiving osimertinib (PFS-OSI). Specifically, it relates to progression of disease according to RECIST 1.1 or death after switching to osimertinib in arms "Gefitinib till + blood test/progression then Osimertinib" and "Gefitinib till progression then Osimertinib". It is formally assessed in these two arms, whilst only provided as a reference for the "Osimertinib till progression" arm, in which progression of disease or death is measured from baseline considering that patients start with osimertinib.
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.
During the PET examination time, a series of arterial blood samples were taken to measure Cmax, %ID brain of \[11C\]osimertinib.
During the PET examination time, a series of arterial blood samples were taken to measure Cmax, SUV brain of \[11C\]osimertinib.
The Tmax, brain was determined directly from the observed concentration versus time data.
The Kp was defined as ratio of radiolabeled drug in brain to that in plasma calculated as area under the brain radioactivity concentration-time curve between 0 and 90 minutes/area under the plasma radioactivity concentration-time curve between 0 and 90 minutes.
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
Part A: To investigate the safety and tolerability of AZD9291 when given in combination with AZD6094 or selumetinib who have progressed following prior therapy with an EGFR TKI agent, and define the combination dose(s) for further clinical evaluation.
Part B: To investigate the safety and tolerability of AZD9291 when given in combination with AZD6094 or selumetinib in patients with locally advanced or metastatic NSCLC, who have progressed on prior therapy with an EGFR TKI agent. Part C monotherapy cohort (Japan only): To investigate and confirm the safety and tolerability of AZD6094 when given orally to Japanese patients with advanced solid malignancies. Part C combination cohort (Japan only): To investigate the safety and tolerability of AZD9291 when given orally to Japanese patients with EGFRm+ NSCLC in combination with AZD6094 who have progressed following prior therapy with an EGFR TKI agent, and define the combination dose(s) for further clinical evaluation. Part D: To investigate the safety and tolerability of AZD9291 when given in combination with AZD6094 (300 mg OD) in patients with locally advanced or metastatic EGFRm+ NSCLC.
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 |
|---|---|---|
| Arm 1: Osimertinib in combination with Datopotamab Deruxtecan | EXPERIMENTAL | Participants in this group will receive osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion q3w of Day 1 of every 21-day cycle. |
| Arm 2: Osimertinib monotherapy | ACTIVE_COMPARATOR | Participants in this group will receive osimertinib 80 mg QD as oral tablet. |
| Osimertinib | EXPERIMENTAL | Participants will receive Osimertinib |
| Placebo | PLACEBO_COMPARATOR | Matching placebo for osimertinib, orally, once daily |
| Treatment Arm A | EXPERIMENTAL | All randomized patients will receive osimertinib 80 mg QD with pemetrexed (500 mg/m\^2) (with pre-treatment) plus either cisplatin (75 mg/m\^2) or carboplatin (\[AUC\] 5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by osimertinib 80 mg QD plus pemetrexed maintenance (500 mg/m\^2) on Day 1 of 21-day cycles |
| Treatment Arm B | PLACEBO_COMPARATOR | All randomized patients will receive placebo QD with pemetrexed (500 mg/m\^2) (with pre-treatment) plus either cisplatin (75 mg/m\^2) or carboplatin (AUC5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by placebo QD plus pemetrexed maintenance (500 mg/m\^2) on Day 1 of 21-day cycles |
| Arm 1: Placebo with platinum-based chemotherapy | PLACEBO_COMPARATOR | Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin) |
| Arm 2: Osimertinib with platinum-based chemotherapy | EXPERIMENTAL | Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin) |
| Arm 3: Osimertinib monotherapy | EXPERIMENTAL | Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) |
| Osimertinib 80mg QD | ACTIVE_COMPARATOR | Osimertinib (AZD9291) 80mg QD. All patients randomized into this will only receive Osimertinib 80mg. Dose may be reduced to allow for the management of IP related toxicity. |
| Osimertinib 80 mg QD and platinum-based chemotherapy | EXPERIMENTAL | Osimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks. Dose may be reduced to allow for the management of IP related toxicity. |
| Placebo Osimertinib | PLACEBO_COMPARATOR | Matching placebo for Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule |
| 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 |
| AZD9291+ placebo | EXPERIMENTAL | AZD9291 (80 mg or 40 mg orally, once daily) plus placebo Erlotinib (150mg or 100mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule. |
| Standard of Care + placebo AZD9291 | ACTIVE_COMPARATOR | Erlotinib (150 mg or 100 mg orally, once daily) or placebo Gefitinib (250 mg orally, once daily) plus placebo AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomisation schedule. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291). |
| Osimertinib as Induction Therapy Prior to Radiotherapy and Maintenance | EXPERIMENTAL | 80 mg Osimertinib QD |
| Open-Label Osimertinib Induction Treatment | EXPERIMENTAL | Patients will receive open-label osimertinib induction treatment for 8 weeks (± 1 week window to account for patient variability and CRT scheduling), followed by CRT treatment for 6 weeks (± 1 week) and then osimertinib maintenance treatment until RECIST 1.1-defined radiological progression by investigator unless there is evidence of unacceptable toxicity or if the patient requests to stop the study treatment. |
| Osimertinib+Amivantamab | EXPERIMENTAL | Participants will receive osimertinib and amivantamab. |
| Treatment Arm | EXPERIMENTAL | First-line treatment = osimertinib, 80 mg, oral, daily; Second-line treatment = platinum (carboplatin or cisplatin) + pemetrexed chemotherapy, prescribed as per institutional standards; Third-line treatment = osimertinib rechallenge, 80 mg, oral, daily. Patients may enter the study at first-line treatment, second-line treatment, or third-line treatment. This is dependent on meeting the eligibility criteria. |
| Arm A | EXPERIMENTAL | Savolitinib 300 mg oral QD Osimertinib 80 mg oral QD |
| Arm B | EXPERIMENTAL | Savolitinib 300 mg oral QD Placebo to Osimertinib 80mg oral QD |
| Module 1: Osimertinib + Savolitinib | EXPERIMENTAL | The patients in this group will receive osimertinib taken in combination with savolitinib |
| Module 2: Osimertinib + Gefitinib | EXPERIMENTAL | The patients in this group will receive osimertinib taken in combination with gefitinib |
| Module 3: Osimertinib + Necitumumab | EXPERIMENTAL | The patients in this group will receive osimertinib taken in combination with necitumumab |
| Module 4: Carboplatin + Pemetrexed + Durvalumab) | EXPERIMENTAL | The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab. |
| Observational Cohort: No study drug | NO_INTERVENTION | Patients in this group will not receive study treatment but receive further anticancer care (Standard of Care therapy or other experimental therapies) or supportive care, as clinically indicated, in accordance with local practice. With Group C, the aim is to understand the clinical course and/or outcome for the overall clinical population after progression on first-line monotherapy with osimertinib. |
| Module 5: Osimertinib + Alectinib | EXPERIMENTAL | The patients in this group will receive osimertinib taken in combination with alectinib |
| Module 6: Osimertinib + Selpercatinib | EXPERIMENTAL | The patients in this group will receive osimertinib taken in combination with selpercatinib |
| Module 7: Etoposide + Durvalumab + Carboplatin or Cisplatin | EXPERIMENTAL | The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab. |
| Module 8: Osimertinib + Pemetrexed + Carboplatin or Cisplatin. | EXPERIMENTAL | The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin). |
| Module 9: Osimertinib + Selumetinib | EXPERIMENTAL | The patients in this group will receive osimertinib taken in combination with selumetinib |
| Module 10: Osimertinib + datopotamab deruxtecan | EXPERIMENTAL | The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan. |
| SRS + Osimertinib | ACTIVE_COMPARATOR | Stereotactic radiotherapy will be delivered in 1-5 fractions to each brain metastases according to the volume and location of the metastases and clinician discretion. Osimertinib will start 1-7 days post radiotherapy. |
| Osimertinib alone | EXPERIMENTAL | Osimertinib 80mg PO daily |
| osimertinib + savolitinib | EXPERIMENTAL | osimertinib + savolitinib |
| placebo + savolitinib | PLACEBO_COMPARATOR | placebo + savolitinib |
| Osimertinib till progression | EXPERIMENTAL | Osimertinib until PD according to RECIST 1.1 |
| Gefitinib till + blood test/progression than Osimertinib | EXPERIMENTAL | Gefitinib until emergence of positive T790M status ("cfDNA T790M positive progression") followed by Osimertinib until second PD according to RECIST 1.1 |
| Gefitinib till progression than Osimertinib | ACTIVE_COMPARATOR | Gefitinib until PD according to RECIST 1.1 followed by Osimertinib until PD according to RECIST 1.1 |
| [11C]osimertinib + oral osimertinib | EXPERIMENTAL | IV microdose administrations of \[11C\]osimertinib co-administered with 80 mg daily oral osimertinib. |
| 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. |
| AZD6094 | EXPERIMENTAL | AZD9291 in combination with AZD6094 |
| Selumetinib | EXPERIMENTAL | AZD9291 in combination with selumetinib |
| MEDI4736 | EXPERIMENTAL | AZD9291 in combination with MEDI4736. Enrolment into the patient cohort that evaluated AZD9291 treatment in combination with MEDI4736 as 1st line treatment has been terminated due to an increased incidence of ILD-like events (interstitial lung disease/pneumonitis), and is no longer being evaluated in this study. |
| AZD6094 (monotherapy) | EXPERIMENTAL | AZD6094 in monotherapy (for Japan only) |
| Daily dose of AZD9291 | EXPERIMENTAL | Daily oral dose of AZD9291 |
| Name | Type | Description |
|---|---|---|
| Osimertinib | DRUG | Osimertinib 80 mg administered orally once daily (QD). |
| Datopotamab Deruxtecan | DRUG | Datopotamab Deruxtecan 6 mg/kg administered as an intravenous (i.v.) infusion every 3 weeks (q3w). |
| Placebo | DRUG | Matching placebo. Initial dose of 80mg once daily can be reduced to 40mg once daily. |
| Osimertinib (AZD9291) pemetrexed cisplatin or carboplatin | DRUG | Randomized patients will receive oral dose of osimertinib with intravenous (IV) pemetrexed plus either IV cisplatin or IV carboplatin |
| Placebo for osimertinib (AZD9291) pemetrexed cisplatin or carboplatin | DRUG | Randomized patients will receive oral dose of placebo matching osimertinib with IV pemetrexed plus either IV cisplatin or IV carboplatin |
| Cisplatin | DRUG | Cisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles. |
| Carboplatin | DRUG | Carboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles |
| Pemetrexed | DRUG | Pemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles |
| Pemetrexed/Carboplatin | DRUG | Drug: Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks. |
| Pemetrexed/Cisplatin | DRUG | Drug: Pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks. |
| Osimertinib 80mg/40mg | DRUG | The initial dose of Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met. |
| Placebo Osimertinib 80mg/40mg | DRUG | The initial dose of Placebo Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met |
| 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 |
| AZD9291 80 mg/40 mg + placebo | DRUG | The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. |
| Placebo Erlotinib 150/100mg | DRUG | The initial dose of Placebo Erlotinib 150 mg once daily can be reduced to Placebo 100 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. |
| Placebo Gefitinib 250 mg | DRUG | The initial dose of Placebo Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. |
| Erlotinib 150/100 mg | DRUG | The initial dose of Erlotinib 150mg once daily can be reduced to 10 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291). |
| Gefitinib 250 mg | DRUG | The initial dose of Gefitinib 250mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291). |
| Placebo AZD9291 80 mg/ 40 mg | DRUG | The initial dose of Placebo AZD9291 80 mg once daily can be reduced to Placebo AZD9291 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. |
| Cisplatin or Carboplatin; Pemetrexed or Paclitaxel | DRUG | Pemetrexed (500 mg/m2 to be administered on Day 1 of every 3-week cycle for 2 cycles) or Paclitaxel (175 mg/m2 on Day 1 of every 3-week cycle for 2 cycles) PLUS Cisplatin (75 mg/m2) or Carboplatin (AUC5) to be administered on Day 1 of every 3--week cycle for 2 cycles |
| Radiation | DRUG | Patients must have received a total dose of radiation of 60 Gy ± 10% (54 to 66 Gy) as part of the chemoradiation therapy. It is recommended but not required that patients have a: * Mean lung dose \< 20 Gy and/or V20 \< 35% * Mean oesophagus dose \< 34 Gy * Heart V50 \< 25%, V30 \< 50%, and V45 \< 35% |
| Amivantamab | DRUG | Amivantamab will be administered as an IV infusion at 1050 mg (\< 80 kg body weight) or 1400mg (≥ 80 kg body weight) (in 28-day cycles: once weekly in Cycle 1 (with a split dose on Days 1 to 2) and then every 2 weeks in subsequent cycles) until progression of disease or until a study intervention discontinuation criterion is met. The first cycle dose is spilt over 2 days- 350 mg on day 1 and 700 mg \[body weight \< 80 kg\] or 1050 mg \[body weight ≥ 80 kg\] on day 2. |
| Osimertinib 80 mg/40 mg | DRUG | Participants will receive osimertinib (80 mg or 40 mg orally, once daily). |
| Osimertinib First-Line | DRUG | Osimertinib, 80 mg, oral, daily |
| Platinum + Pemetrexed Chemotherapy Second-Line | DRUG | Platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed are prescribed as per institutional standards. |
| Osimertinib Third-Line | DRUG | Rechallenge with osimertinib, 80 mg, oral, daily |
| Osimertinib + Savolitinib | DRUG | Osimertinib 80 mg oral QD Savolitinib 300mg oral QD |
| Savolitinib + Placebo | DRUG | Savolitinib 300mg Oral QD Placebo to Osimertinib 80mg oral QD |
| Savolitinib | DRUG | Savolitinib will be given orally at 300 mg or 600mg once daily |
| Gefitinib | DRUG | Gefitinib given orally at 250 mg once daily |
| Necitumumab | DRUG | Necitumumab given IV at 800 mg on Day 1 and Day 8 of every 3-week cycle |
| Durvalumab | DRUG | Durvalumab given IV at 1500 mg on Day 1 of every cycle |
| Alectinib | DRUG | Alectinib given orally at 600mg twice daily and for Japanese patients at 300mg twice daily. |
| Selpercatinib | DRUG | Selpercatinib given orally at 160mg twice daily |
| Selumetinib | DRUG | Selumetinib given orally at 75 mg twice daily for 4 days, followed by 3 days off treatment |
| Etoposide | DRUG | Etoposide 80-100 mg/m2 given IV on day 1, 2 and 3 of every 21-day cycle for up to 4 cycles. |
| Stereotactic radiotherapy | RADIATION | 1-5 fractions of stereotactic radiotherapy |
| [11C]osimertinib | DRUG | Patients will receive 3 single IV microdose administrations of \[11C\]osimertinib and PET exams on: Day 1, Day 2 (or up to Day 8) and Day 29. |
| 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 |
| Part A - AZD9291 in combination with AZD6094 | DRUG | Part A - AZD9291 and AZD6094 administered in different doses to investigate the safety and tolerability of this combination and define the combination dose for further clinical evaluation in Part B. |
| Part A - AZD9291 in combination with continuous selumetinib (Asian subjects) | DRUG | Part A - AZD9291 and selumetinib (continuous treatment) administered in different doses to investigate the safety and tolerability of this combination in Asian subjects and to define the combination dose for further clinical evaluation in Part B. |
| Part A - AZD9291 in combination with continuous selumetinib (non-Asian subjects) | DRUG | Part A - AZD9291 and selumetinib (continuous treatment) administered in different doses to investigate the safety and tolerability of this combination in non-Asian subjects and to define the combination dose for further clinical evaluation in Part B. |
| Part A - AZD9291 in combination with intermittent selumetinib | DRUG | Part A - AZD9291 and selumetinib (intermittent treatment) administered in different doses to investigate the safety and tolerability of this combination and to define the combination dose for further clinical evaluation in Part B. |
| Part A - AZD9291 in combination with MEDI4736 | DRUG | Part A - AZD9291 and MEDI4736 administered in different doses to investigate the safety and tolerability of this combination and to define the combination dose for further clinical evaluation in Part B. Note: Enrolment into the patient cohort that evaluated AZD9291 treatment in combination with MEDI4736 as 1st line treatment has been terminated due to an increased incidence of ILD-like events (interstitial lung disease/pneumonitis), and is no longer being evaluated in this study. |
| Part B - AZD9291 in combination with AZD6094 | DRUG | Part B - AZD9291 and AZD6094 administered in the dose identified in Part A (AZD9291 80mg OD + AZD6094 600mg OD) to further investigate the safety and tolerability of this combination. |
| Part B - AZD9291 in combination with selumetinib | DRUG | Part B - AZD9291 and selumetinib administered in the dose identified in Part A (AZD9291 80mg OD + selumetinib 75 mg BD intermittent \[4 days on/3 days off\]) to further investigate the safety and tolerability of this combination. |
| Part B - AZD9291 in combination with MEDI4736 | DRUG | Part B - AZD9291 and MEDI4736 administered in the dose identified in Part A to further investigate the safety and tolerability of this combination. Note: Enrolment into the patient cohort that evaluated AZD9291 treatment in combination with MEDI4736 as 1st line treatment has been terminated due to an increased incidence of ILD-like events (interstitial lung disease/pneumonitis), and is no longer being evaluated in this study. |
| Part C - AZD6094 monotherapy (Japan only) | DRUG | Part C - AZD6094 monotherapy to assess the safety, tolerability and pharmacokinetics of the monotherapy of AZD6094 in Japanese patients with advanced NSCLC. |
| Part C - AZD9291 in combination with AZD6094 (Japan only) | DRUG | Part C combination cohort - AZD9291 80mg OD administered in combination with AZD6094 400mg OD (AZD6094 dose in which DLTs have not been identified in the Japanese monotherapy cohort) in order to confirm the safety, tolerability, pharmacokinetics and preliminary anti-tumor activities of this combination in Japanese subjects. The 400mg OD dosing schedule will be initiated in the first cohort. The dose may be subsequently reduced in further cohorts in response to emerging safety, or PK findings or other reasons identified in the savolitinib programme. |
| Part D - AZD9291 in combination with AZD6094 | DRUG | Part D - AZD9291 80mg OD administered in combination with AZD6094 300mg OD to further evaluate the safety, tolerability, pharmacokinetics and antitumor activity in terms of ORR and PFS in patients with locally advanced or metastatic cMET positive EGFRm+ and T790M-negative NSCLC, following progression on EGFR-TKI treatment. The choice of AZD6094 dose of 300 mg is based on results from preclinical and clinical studies. Clinical testing of the 300 mg OD dose will enable better assessment of impact of lower AZD6094 exposure on overall tolerability and hepatotoxicity risk as well as exploration of the efficacy and overall safety profiles with a dose meaningfully lower than the current dose of 600 mg OD. |
Inclusion Criteria: Age 1. Participant must be ≥ 18 years. Type of Participant and Disease Characteristics 2. Histologically or cytologically documented nonsquamous NSCLC. NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC...
Top 2 of 4 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| GE Healthcare Technologies Inc. | GEHC | 1 | PHASE1 | GEH200520/GEH200521 |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | Olverembatinib |
Osimertinib is a small molecule EGFR inhibitor developed by AstraZeneca PLC (ticker AZN) for oncology. It is being studied in EGFR mutation positive non-small cell lung cancer, including locally advanced or metastatic disease and EGFR sensitising mutation positive NSCLC. It is an investigational therapy in clinical development.
Osimertinib is being evaluated for EGFR mutation positive non-small cell lung cancer, including locally advanced or metastatic disease and EGFR sensitising mutation positive NSCLC. It is also studied in advanced NSCLC, carcinoma, and broader cancer settings. It is not approved for these uses and remains in clinical development.
Osimertinib targets EGFR, the epidermal growth factor receptor, and acts as an inhibitor. This mechanism is relevant to EGFR mutation positive non-small cell lung cancer, where EGFR mutations drive tumor growth. Osimertinib is a small molecule developed by AstraZeneca PLC.
Osimertinib is developed by AstraZeneca PLC, which trades under the ticker AZN. AstraZeneca is the sponsor of the clinical trials evaluating Osimertinib in EGFR mutation positive non-small cell lung cancer and related indications.
Osimertinib is in Phase 1 development according to the current pipeline data, with additional Phase 2 and Phase 3 trials ongoing. It is investigational and has not been approved for the indications studied. The program includes 14 trials, with 10 active and 3 completed, enrolling 3,204 participants in total.
Osimertinib is being studied in several trials, including NCT07295821, a Phase 2 induction and maintenance study in chemo-ineligible stage III unresectable EGFR+ NSCLC; NCT06350097, a Phase 3 study with or without datopotamab deruxtecan; NCT06194448, a Phase 2 study prior to CRT and maintenance; and NCT05801029, a Phase 2 study with amivantamab.
Yes, Osimertinib is also known as AZD9291. Other alternative names include Osimertinib + Savolitinib, Osimertinib 80 mg/40 mg, and AZD9291 tablets. These names refer to the same investigational EGFR inhibitor developed by AstraZeneca PLC.