| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT06350097 | Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer | PHASE3 | RECRUITING | 582 | — | — | Apr 29, 2024 | Aug 29, 2031 | May 6, 2026 | 166 | United States, Australia +17 |
| NCT05120349 | A Global Study to Assess the Effects of Osimertinib in Participants With EGFRm Stage IA2-IA3 NSCLC Following Complete Tumour Resection | PHASE3 | ACTIVE NOT_RECRUITING | 390 | — | — | Feb 21, 2022 | Nov 1, 2032 | Apr 23, 2026 | 139 | United States, Argentina +18 |
| NCT04351555 | A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer | PHASE3 | ACTIVE NOT_RECRUITING | 358 | — | — | Dec 16, 2020 | Jun 13, 2029 | Jun 5, 2026 | 158 | United States, Austria +23 |
| NCT04035486 | A 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 | 587 | — | — | Jul 2, 2019 | Dec 22, 2026 | Oct 10, 2025 | 153 | United States, Argentina +19 |
| NCT05546866 | Study to Assess the Efficacy and Safety of Adjuvant Osimertinib in NSCLC With Uncommon EGFRm | PHASE2 | ACTIVE NOT_RECRUITING | 51 | — | — | Feb 9, 2023 | Jun 30, 2029 | May 13, 2026 | 10 | China |
| NCT04606771 | A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients With EGFRm+ and MET Amplified Advanced NSCLC | PHASE2 | ACTIVE NOT_RECRUITING | 30 | — | — | Sep 28, 2020 | Mar 30, 2026 | Feb 27, 2026 | 21 | United States, Argentina +4 |
| NCT03944772 | Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD) | PHASE2 | ACTIVE NOT_RECRUITING | 247 | — | — | Jun 25, 2019 | May 6, 2025 | Jan 30, 2025 | 47 | United States, Denmark +7 |
| NCT02442349 | Phase II Single Arm Study of AZD9291 to Treat NSCLC Patients in Asia Pacific | PHASE2 | COMPLETED | 171 | — | — | Jun 22, 2015 | Nov 28, 2025 | Jan 9, 2026 | 30 | Australia, China +1 |
| NCT03463525 | Open-label PET Study With [11C]Osimertinib in Patients With EGFRm NSCLC and Brain Metastases | PHASE1 | COMPLETED | 4 | — | — | Oct 24, 2018 | Oct 5, 2020 | Jan 27, 2023 | 1 | Sweden |
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).
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.
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.
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
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.
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.
| 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 | Osimertinib 80mg, orally, once daily (Dose may be reduced to 40 mg once daily if required at the discretion of the investigator) |
| Placebo | PLACEBO_COMPARATOR | Matching placebo for osimertinib, orally, once daily |
| 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. |
| 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. |
| AZD9291 | EXPERIMENTAL | Once daily tablet 80 mg |
| [11C]osimertinib + oral osimertinib | EXPERIMENTAL | IV microdose administrations of \[11C\]osimertinib co-administered with 80 mg daily oral osimertinib. |
| 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. |
| 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 + 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. |
| AZD9291 | DRUG | Once daily tablet 80 mg |
| [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. |
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...