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Osimertinib

Phase 3

Non-Small Cell Lung Cancer | Small molecule | Oncology |AstraZeneca PLC|Last Updated: Jun 5, 2026

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindNO_TREATMENT_CONTROLLEDDMCBiomarker
Total Trials9
Total Enrollment2,420
FDA Designations
PRIORITY_REVIEW
Clinical Trials (9)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT06350097Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung CancerPHASE3 RECRUITING 582Apr 29, 2024Aug 29, 2031May 6, 2026166 United States, Australia +17
NCT05120349A Global Study to Assess the Effects of Osimertinib in Participants With EGFRm Stage IA2-IA3 NSCLC Following Complete Tumour ResectionPHASE3 ACTIVE NOT_RECRUITING 390Feb 21, 2022Nov 1, 2032Apr 23, 2026139 United States, Argentina +18
NCT04351555A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung CancerPHASE3 ACTIVE NOT_RECRUITING 358Dec 16, 2020Jun 13, 2029Jun 5, 2026158 United States, Austria +23
NCT04035486A Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)PHASE3 ACTIVE NOT_RECRUITING 587Jul 2, 2019Dec 22, 2026Oct 10, 2025153 United States, Argentina +19
NCT05546866Study to Assess the Efficacy and Safety of Adjuvant Osimertinib in NSCLC With Uncommon EGFRmPHASE2 ACTIVE NOT_RECRUITING 51Feb 9, 2023Jun 30, 2029May 13, 202610 China
NCT04606771A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients With EGFRm+ and MET Amplified Advanced NSCLCPHASE2 ACTIVE NOT_RECRUITING 30Sep 28, 2020Mar 30, 2026Feb 27, 202621 United States, Argentina +4
NCT03944772Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)PHASE2 ACTIVE NOT_RECRUITING 247Jun 25, 2019May 6, 2025Jan 30, 202547 United States, Denmark +7
NCT02442349Phase II Single Arm Study of AZD9291 to Treat NSCLC Patients in Asia PacificPHASE2 COMPLETED 171Jun 22, 2015Nov 28, 2025Jan 9, 202630 Australia, China +1
NCT03463525Open-label PET Study With [11C]Osimertinib in Patients With EGFRm NSCLC and Brain MetastasesPHASE1 COMPLETED 4Oct 24, 2018Oct 5, 2020Jan 27, 20231 Sweden
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Study Endpoints
Primary Endpoints
To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Progression Free Survival (PFS) by BICR in all randomised participants.
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.

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).

Disease-Free Survival (DFS) in high-risk stratum
From date of randomisation up to approximately 10 years

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.

Major Pathological Response (MPR) - IASLC Method
From date of randomization to an average of 12 weeks after the first dose

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.

Major Pathological Response (MPR) - Chemotherapy Method
From date of randomization to an average of 12 weeks after the first dose

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 Graded by Common Terminology Criteria for Adverse Event v5 (Safety Run-In Treatment Arms Only)
From first dose date to 28 days following last dose, up to 45 months

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) (Randomized Component)
Up to approximately 33 months after the first patient is randomized (maximum follow up of 33.3 months)

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) Assessment (Randomized Component)
Up to approximately 33 months after the first patient is randomized (maximum follow up of 33.2 months).

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.

3-year disease-free survival (DFS) rate by investigator assessment
Up to 3 years for each subject from the first dosing of study treatment.

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 (ORR)
Tumour assessments every 6 weeks from randomisation up to 24 weeks, then every 8 weeks until objective disease progression (maximum of approximately 25 months)

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.

ORR According to RECIST 1.1 by Independent Review
At baseline and every 6 weeks from time of first dose until objective disease progression,up to 24 months after Last Patient First Dose(LPFD)

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.

Maximum Concentration of Percent of Injected Dose in the Whole Brain (Cmax, %ID Brain) of [11C]Osimertinib
Day 1, Day 2 (or up to Day 8) and Day 25

During the PET examination time, a series of arterial blood samples were taken to measure Cmax, %ID brain of \[11C\]osimertinib.

Maximum Concentration of Brain Standardized Uptake Value (Cmax, SUV Brain) of [11C]Osimertinib
Day 1, Day 2 (or up to Day 8) and Day 25

During the PET examination time, a series of arterial blood samples were taken to measure Cmax, SUV brain of \[11C\]osimertinib.

Time of Maximum Radioactivity Concentration in the Brain (Tmax, Brain) of [11C]Osimertinib
Day 1, Day 2 (or up to Day 8) and Day 25

The Tmax, brain was determined directly from the observed concentration versus time data.

Brain to Plasma Partition Coefficient (Kp) of [11C]Osimertinib
Day 1, Day 2 (or up to Day 8) and Day 25

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.

Secondary Endpoints
To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Survival (OS) in all randomised participants.
It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS on Central nervous system (CNS) metastases in participants with CNS metastases at baseline
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by investigator in all randomised participants.
It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Arm 1: Osimertinib in combination with Datopotamab DeruxtecanEXPERIMENTALParticipants 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 monotherapyACTIVE_COMPARATORParticipants in this group will receive osimertinib 80 mg QD as oral tablet.
OsimertinibEXPERIMENTALOsimertinib 80mg, orally, once daily (Dose may be reduced to 40 mg once daily if required at the discretion of the investigator)
PlaceboPLACEBO_COMPARATORMatching placebo for osimertinib, orally, once daily
Arm 1: Placebo with platinum-based chemotherapyPLACEBO_COMPARATORPlacebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)
Arm 2: Osimertinib with platinum-based chemotherapyEXPERIMENTALOsimertinib 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 monotherapyEXPERIMENTALOsimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)
Osimertinib 80mg QDACTIVE_COMPARATOROsimertinib (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 chemotherapyEXPERIMENTALOsimertinib 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.
Arm AEXPERIMENTALSavolitinib 300 mg oral QD Osimertinib 80 mg oral QD
Arm BEXPERIMENTALSavolitinib 300 mg oral QD Placebo to Osimertinib 80mg oral QD
Module 1: Osimertinib + SavolitinibEXPERIMENTALThe patients in this group will receive osimertinib taken in combination with savolitinib
Module 2: Osimertinib + GefitinibEXPERIMENTALThe patients in this group will receive osimertinib taken in combination with gefitinib
Module 3: Osimertinib + NecitumumabEXPERIMENTALThe patients in this group will receive osimertinib taken in combination with necitumumab
Module 4: Carboplatin + Pemetrexed + Durvalumab)EXPERIMENTALThe patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab.
Observational Cohort: No study drugNO_INTERVENTIONPatients 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 + AlectinibEXPERIMENTALThe patients in this group will receive osimertinib taken in combination with alectinib
Module 6: Osimertinib + SelpercatinibEXPERIMENTALThe patients in this group will receive osimertinib taken in combination with selpercatinib
Module 7: Etoposide + Durvalumab + Carboplatin or CisplatinEXPERIMENTALThe 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.EXPERIMENTALThe patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).
Module 9: Osimertinib + SelumetinibEXPERIMENTALThe patients in this group will receive osimertinib taken in combination with selumetinib
Module 10: Osimertinib + datopotamab deruxtecanEXPERIMENTALThe patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan.
AZD9291EXPERIMENTALOnce daily tablet 80 mg
[11C]osimertinib + oral osimertinibEXPERIMENTALIV microdose administrations of \[11C\]osimertinib co-administered with 80 mg daily oral osimertinib.
Interventions
NameTypeDescription
OsimertinibDRUGOsimertinib 80 mg administered orally once daily (QD).
Datopotamab DeruxtecanDRUGDatopotamab Deruxtecan 6 mg/kg administered as an intravenous (i.v.) infusion every 3 weeks (q3w).
PlaceboDRUGMatching placebo. Initial dose of 80mg once daily can be reduced to 40mg once daily.
CisplatinDRUGCisplatin (75mg/m2) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles.
CarboplatinDRUGCarboplatin (AUC5) to be administered with pemetrexed on Day 1 of every 3-week cycle for 3 cycles
PemetrexedDRUGPemetrexed (500 mg/m2) to be administered with cisplatin or carboplatin on Day 1 of every 3-week cycle for 3 cycles
Pemetrexed/CarboplatinDRUGDrug: 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/CisplatinDRUGDrug: 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 + SavolitinibDRUGOsimertinib 80 mg oral QD Savolitinib 300mg oral QD
Savolitinib + PlaceboDRUGSavolitinib 300mg Oral QD Placebo to Osimertinib 80mg oral QD
SavolitinibDRUGSavolitinib will be given orally at 300 mg or 600mg once daily
GefitinibDRUGGefitinib given orally at 250 mg once daily
NecitumumabDRUGNecitumumab given IV at 800 mg on Day 1 and Day 8 of every 3-week cycle
DurvalumabDRUGDurvalumab given IV at 1500 mg on Day 1 of every cycle
AlectinibDRUGAlectinib given orally at 600mg twice daily and for Japanese patients at 300mg twice daily.
SelpercatinibDRUGSelpercatinib given orally at 160mg twice daily
SelumetinibDRUGSelumetinib given orally at 75 mg twice daily for 4 days, followed by 3 days off treatment
EtoposideDRUGEtoposide 80-100 mg/m2 given IV on day 1, 2 and 3 of every 21-day cycle for up to 4 cycles.
AZD9291DRUGOnce daily tablet 80 mg
[11C]osimertinibDRUGPatients 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.
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites166

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...

Countries:United StatesAustraliaBrazilCanadaChinaFranceGermanyHong KongIndiaItalyJapanPolandPuerto RicoSouth KoreaSpainTaiwanThailandTurkey (Türkiye)VietnamArgentinaMalaysiaRomaniaRussiaSingaporeUnited KingdomAustriaBulgariaChileIsraelMexicoPeruSwitzerlandCzechiaPhilippinesSlovakiaSouth AfricaDenmarkNetherlandsNorwaySweden
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Competitive Landscape -Non-Small Cell Lung Cancer 406 trials
CompanyTickerTrialsLead PhaseDrugs
Merck & Co., Inc.MRK25PHASE3Pembrolizumab, Olaparib, Etoposide, Carboplatin, Cisplatin
Amgen Inc.AMGN5PHASE3AMG 510, Docetaxel, ABP 234, Pembrolizumab, Sotorasib
AstraZeneca PLCAZN63PHASE3Datopotamab deruxtecan, Durvalumab, Carboplatin, Pembrolizumab, Cisplatin
Revolution Medicines, Inc.RVMD8PHASE3daraxonrasib, docetaxel, RMC-6291, Elironrasib, Daraxonrasib
Eli Lilly and CompanyLLY19PHASE3Selpercatinib, Carboplatin, Cisplatin, Pemetrexed, Pembrolizumab
AbbVie, Inc.ABBV10PHASE3Telisotuzumab Vedotin, Docetaxel, Telisotuzumab vedotin, Telisotuzumab Adizutecan, Livmoniplimab
Bristol-Myers Squibb CompanyBMY20PHASE3Repotrectinib, Crizotinib, Nivolumab, Carboplatin, Cisplatin
BioNTech SE Sponsored ADRBNTX7PHASE3Gotistobart, Docetaxel, PM8002, Carboplatin, Pemetrexed
Gilead Sciences, Inc.GILD4PHASE3Sacituzumab Govitecan-hziy, Docetaxel, Zimberelimab, Domvanalimab, Pembrolizumab
GSK plc Sponsored ADRGSK4PHASE3Cobolimab, Dostarlimab, Docetaxel, Belrestotug, Pembrolizumab
Johnson & JohnsonJNJ18PHASE3Lazertinib, Amivantamab, Pemetrexed, Carboplatin, Osimertinib
Pfizer Inc.PFE21PHASE3Lorlatinib, Crizotinib, Avelumab, Lorlatanib, Talazoparib
ArriVent BioPharma, Inc.AVBP9PHASE3Firmonertinib, Drug: Furmonertinib, Furmonertinib, JAB-21822, JAB 21822
Novartis AG Sponsored ADRNVS9PHASE3JDQ443, docetaxel, TNO155, tislelizumab, DKY709
Summit Therapeutics IncSMMT2PHASE3Ivonescimab, Pembrolizumab
Nuvation Bio, Inc. Class ANUVB4PHASE3Taletrectinib, Crizotinib, AB-106
Genmab A/S Sponsored ADRGMAB4PHASE3Acasunlimab, Pembrolizumab, Docetaxel, Rina-S, GEN1042
Incyte CorporationINCY1PHASE3Retifanlimab, Pemetrexed, Cisplatin, Carboplatin, Paclitaxel
Regeneron Pharmaceuticals, Inc.REGN6PHASE2cemiplimab, Platinum Doublet, fianlimab, Pemetrexed, Paclitaxel
BeOne Medicines Ltd. Sponsored ADRONC6PHASE3Tislelizumab, Cisplatin, Paclitaxel, Pemetrexed Disodium, Carboplatin
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Recent Changes (Last 90 Days)
LOWJun 5, 2026NCT04351555lastUpdatePostDate: changed
LOWJun 5, 2026NCT04351555lastUpdatePostDate: changed
LOWJun 5, 2026NCT04351555lastUpdatePostDate: changed
LOWJun 5, 2026NCT04351555lastUpdatePostDate: changed
MEDIUMMay 26, 2026NCT06350097primaryCompletionDate: changed
LOWMay 26, 2026NCT04035486primaryCompletionDate: changed
LOWMay 26, 2026NCT04606771primaryCompletionDate: changed
LOWMay 26, 2026NCT05120349primaryCompletionDate: changed
LOWMay 26, 2026NCT05546866primaryCompletionDate: changed
LOWMay 26, 2026NCT04351555primaryCompletionDate: changed
LOWMay 26, 2026NCT03944772primaryCompletionDate: changed
LOWMay 24, 2026NCT06350097studyFirstPostDate: changed
LOWMay 24, 2026NCT04606771studyFirstPostDate: changed
LOWMay 24, 2026NCT04035486studyFirstPostDate: changed
LOWMay 24, 2026NCT05120349studyFirstPostDate: changed
LOWMay 24, 2026NCT05546866studyFirstPostDate: changed
LOWMay 24, 2026NCT04351555studyFirstPostDate: changed
LOWMay 24, 2026NCT03944772studyFirstPostDate: changed