T790M-positive Advanced NSCLC Research Articles

Efficacy and Safety of SH-1028 in Patients With EGFR T790M-Positive NSCLC: A Multicenter, Single-Arm, Open-Label, Phase 2 Trial

IntroductionAs a novel third-generation EGFR tyrosine kinase inhibitor (TKI), SH-1028 (formerly oritinib) is developed to inhibit both sensitizing EGFR mutations and EGFR T790M mutation. MethodsThis was a multicenter, single-arm, open-label, phase 2 trial (NCT03823807). Eligible patients were those with advanced NSCLC with centrally confirmed EGFR T790M mutation who progressed after first- or second-generation EGFR TKIs or with primary EGFR T790M mutations. Each patient received SH-1028 tablets orally at 200 mg/d until disease progression or intolerable toxicity. Tumor response was evaluated every 6 weeks per the Response Evaluation Criteria in Solid Tumors, version 1.1. The primary end point was objective response rate by an independent review committee. The secondary end points were progression-free survival, overall survival (OS), disease control rate, safety, and so on. ResultsA total of 286 patients with EGFR T790M-positive advanced NSCLC were enrolled in this study, including 59 patients in part A (dose-verification study) and 227 patients in part B (second-line registration study). By data cutoff on September 17, 2021, the independent review committee–assessed objective response rate was 55.9% (95% confidence interval [CI]: 42.4–68.8) in part A and 60.4% (95% CI: 53.7–66.8) in part B. The median progression-free survival was 12.4 months (95% CI: 8.3–20.8) in part A and 12.6 months (95% CI: 9.7–15.3) in part B. The median OS was 26.0 months (95% CI: 23.3–not reached) in part A, and OS was immature in part B. Among the 286 patients, 44 of them experienced at least one grade 3 or higher treatment-related adverse event, with the most common ones as increased serum creatinine phosphokinase level (13 [4.5%]), diarrhea (six [2.1%]), and prolonged QT interval (three [1.0%]). Treatment-related skin rash was reported in 26 patients (9.1%), all grade 1 or 2. There was no interstitial lung disease reported in this study. ConclusionsSH-1028 is efficacious and tolerable in second-line treatment of patients with advanced NSCLC with positive EGFR T790M.

7MO Oritinib (SH-1028) a third-generation EGFR tyrosine kinase inhibitor in locally advanced or metastatic NSCLC patients with positive EGFR T790M: Results of a single-arm phase II trial

Oritinib (SH-1028) is a third-generation EGFR-TKI selectively targeting both sensitive EGFR and EGFR T790M mutations. Herein, we report the efficacy and safety of oritinib in EGFR T790M-positive advanced NSCLC patients from the phase II study (NCT03823807). Eligible patients were locally advanced or metastatic NSCLC patients aged ≥ 18 years, with centrally confirmed EGFR T790M mutation. Patients with asymptomatic, stable CNS metastases were eligible into the study. Oritinib 200 mg was given orally once daily until disease progression or unacceptable toxicity. Primary efficacy endpoint was objective response rate (ORR). Secondary efficacy endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Between December 2019 and March 2021, 228 patients were enrolled and 227 patients received at least one dose of oritinib. The median age of 227 patients was 62 years old, 57.3% of patients were female and 24.7% received systemic chemotherapies. At data cutoff (September 17, 2021), 137 of 227 patients achieved confirmed partial responses with ORR of 60.4% (95% CI: 42.4%, 68.8%) by IRaC. The DCR was 92.5% (88.3%, 95.6%), the mPFS was 12.6 months (95% CI: 9.7, 15.3), the mDOR was 12.5 months (95% CI: 11.2, NA) and the mOS was immature. The most common (≥10%) treatment-emergent adverse events (TEAEs) included diarrhea (45.4%), increased blood creatine phosphokinase (26.0%), anaemia (20.3%), decreased white blood cell count (15.4%), decreased appetite (15.0%), increased blood creatine phosphokinase isoenzyme (13.2%), nausea (13.2%), vomiting (13.2%), increased serum creatine (12.8%), upper respiratory tract infection (12.3%), increased aspartate aminotransferase (11.9%), cough(11.9%), decreased platelet count (11.0%), constipation (10.6%). Grade≥3 TEAEs included increased blood creatine phosphokinase (4.0%), hypertension (3.1%), death (2.6%), diarrhea (2.2%). No interstitial lung disease were reported. Oritinib demonstrated potential clinical benefit and tolerable in advanced NSCLC patients with EGFR T790M mutation.

Efficacy of Aumolertinib (HS-10296) in Patients With Advanced EGFR T790M+ NSCLC: Updated Post-National Medical Products Administration Approval Results From the APOLLO Registrational Trial

IntroductionAumolertinib (formerly almonertinib; HS-10296) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) with revealed activity against EGFR-sensitizing mutations and EGFR T790M mutation. MethodsPatients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy were enrolled in this registrational phase 2 trial of aumolertinib at 110 mg orally once daily (NCT02981108). The primary end point was objective response rate (ORR) by independent central review. ResultsA total of 244 patients with EGFR T790M-positive NSCLC were enrolled. The ORR by independent central review was 68.9% (95% confidence interval [CI]: 62.6–74.6). The disease control rate was 93.4% (95% CI: 89.6–96.2). The median duration of response was 15.1 months (95% CI: 12.5–16.6). The median progression-free survival was 12.4 months (95% CI: 9.7–15.0). Among 23 patients with assessable central nervous system (CNS) metastases, the CNS-ORR and CNS-disease control rate were 60.9% (95% CI: 38.5–80.3) and 91.3% (95% CI: 72.0–98.9), respectively. The median CNS-duration of response was 12.5 months (95% CI: 5.6–not reached). Treatment-related adverse events of more than or equal to grade 3 occurred in 16.4% of the patients, with the most common being increased blood creatine phosphokinase level (7%) and increased alanine aminotransferase level (1.2%). The relative dose density of aumolertinib was 99.2% in this study. ConclusionsAumolertinib is an effective and well-tolerated third-generation EGFR TKI for patients with EGFR T790M-positive advanced NSCLC after disease progression on first- and second-generation EGFR TKI therapy. On the basis of these findings, aumolertinib was approved in the People’s Republic of China for patients positive for EGFR T790M NSCLC.

FP14.14 Post Hoc Analyses from an Open Label, Multi-Centre, ASTRIS Trial of Efficacy of Osimertinib for CNS Metastases with T790M-Positive Advanced NSCLC

FP14.14 Post Hoc Analyses from an Open Label, Multi-Centre, ASTRIS Trial of Efficacy of Osimertinib for CNS Metastases with T790M-Positive Advanced NSCLC

P76.39 Acquired Resistance Mechanisms in T790M-Positive Advanced NSCLC Tested by Non-Invasive Molecular Testing (NIMT) and Their Clinical Relevance

P76.39 Acquired Resistance Mechanisms in T790M-Positive Advanced NSCLC Tested by Non-Invasive Molecular Testing (NIMT) and Their Clinical Relevance

Integrated histological and molecular analyses of rebiopsy samples at osimertinib progression improve post-progression survivals: A single-center retrospective study

BackgroundThis single-center retrospective cohort study sought to investigate the impact of rebiopsy analysis after osimertinib progression in improving the survival outcomes. MethodsEighty-nine patients with EGFR T790M-positive advanced NSCLC who received second- or further-line osimertinib between January 2017 and July 2019 were included in this study. The co-primary study endpoints were post-progression progression-free survival (pPFS), defined as the time from osimertinib progression until progression from further-line treatment, and post-progression overall survival (pOS), defined as the time from osimertinib progression until death or the last follow-up date. ResultsPairwise analysis revealed that receiving targeted therapy as further-line treatment after osimertinib progression did not statistically improve the pPFS (P = 0.285) or the pOS (P = 0.903) compared to chemotherapy. However, patients who submitted rebiopsy samples at osimertinib progression for histological and molecular analyses, particularly those who had actionable markers and received highly matched therapy, had significantly longer pPFS and pOS as compared to those who received low-level matched therapy (pPFS = 10.0 m vs. 4.1 m, P = 0.005; pOS = 19.4 m vs. 10.0 m, P = 0.023), unmatched therapy (pPFS = 10.0 m vs. 4.7 m, P = 0.009; pOS = 19.4 m vs. 7.0 m, P = 0.001), and those without rebiopsy data (Rebiopsy vs Non-rebiopsy; pPFS = 6.1 m vs. 3.3 m, P = 0.014; pOS = 11.7 m vs. 6.8 m, P = 0.011). ConclusionOur real-world cohort study demonstrates that integrated histological and molecular analyses of rebiopsy specimens after osimertinib progression could provide more opportunities for individualized treatments to improve the post-progression survival of patients with advanced NSCLC. Our findings provide clinical evidence that supports the inclusion of NGS-based analysis of rebiopsy specimens as standard-of-care after osimertinib progression and warrants further prospective evaluation.

Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: The AURA Leptomeningeal Metastases Analysis.

Osimertinib has shown promising activity in patients with leptomeningeal metastases (LMs) of EGFR-positive NSCLC at 160 mg once daily (qd) (BLOOM; NCT02228369). We report LM activity with osimertinib (80 mg qd) in a retrospective analysis of studies across the AURA program (AURA extension, AURA2, AURA17, and AURA3). Patients with EGFR T790M-positive advanced NSCLC and progression after previous EGFR-tyrosine kinase inhibitor therapy received osimertinib (80 mg qd). Patients with central nervous system (CNS) metastases (including LMs) were eligible if the lesions were neurologically asymptomatic and stable. Patients with evidence of LMs at the study entry were retrospectively included for the analysis; brain scans were assessed for radiologic LM response by neuroradiologically blinded, independent central review per the modified Response Assessment in Neuro-Oncology LM criteria. LM objective response rate, duration of response, progression-free survival, and overall survival were assessed. A longitudinal analysis was performed to investigate the relationship between changes from the baseline in non-CNS tumor sizes and LM responses at each visit of patients in AURA LM and BLOOM studies. For the 22 patients included in the analysis, LM objective response rate was 55% (95% confidence interval [CI]: 32-76). Median LM duration of response was not reached (95% CI: 2.8-not calculable [NC]). Median LM progression-free survival and overall survival were 11.1 months (95% CI: 4.6-NC) and 18.8 months (95% CI: 6.3-NC), respectively. The longitudinal analysis revealed similar non-CNS and LM responses between the patients in AURA LM and BLOOM programs. Patients with EGFR T790M-positive NSCLC and radiologically detected LM obtained clinical benefit from osimertinib (80 mg qd).

P1.13-25 Efficacy and Safety of Osimertinib in EGFR T790M-Positive Advanced NSCLC Patients with Brain Metastases (APOLLO Study)

P1.13-25 Efficacy and Safety of Osimertinib in EGFR T790M-Positive Advanced NSCLC Patients with Brain Metastases (APOLLO Study)

P2.04-006 ADAURA: PhIII, Double-Blind, Randomized Study of Osimertinib vs Placebo in EGFR Mutation-Positive NSCLC Post-Tumor Resection

EGFR-TKIs are standard first-line therapy in patients with EGFR sensitizing mutation (EGFRm)-positive advanced NSCLC. EGFR T790M resistance mutation is observed in >50% of patients with acquired resistance to EGFR-TKIs. Osimertinib is a third-generation, irreversible, CNS-active EGFR-TKI selective for EGFRm and T790M, recommended in patients with T790M-positive advanced NSCLC who have progressed on first-line EGFR-TKIs. In a recent study (NCT01405079), gefitinib treatment in patients with resected EGFRm-positive NSCLC significantly increased disease-free survival (DFS) vs vinorelbine+cisplatin: median 28.7 vs 18.0 months (hazard ratio 0.60 (95% CI 0.42–0.87), p=0.005), warranting further investigation of EGFR-TKIs in this setting (Wu et al, J Clin Oncol 2017;35:suppl;abs8500).

1353P - CNS response to osimertinib in Asian-Pacific patients (pts) with T790M-positive advanced NSCLC: data from an open-label Phase II trial (AURA17)

Background: Osimertinib has shown CNS efficacy in a pooled analysis of two Phase II trials (AURA extension: NCT01802632, AURA2: NCT02094261) in pts with T790M-positive advanced NSCLC. We report osimertinib efficacy in CNS metastases (mets) from a Phase II, open-label, single-arm trial (AURA17: NCT02442349) in Asia-Pacific pts with T790M-positive advanced NSCLC who had progressed on prior EGFR-TKI therapy, with or without additional anti-cancer regimens. Methods: Pts with stable, asymptomatic, CNS mets were eligible for enrolment and received osimertinib 80 mg once daily. This prespecified subgroup analysis was conducted in pts with CNS mets present on baseline brain scan as assessed by blinded independent central neuroradiology review (BICR). Endpoints included CNS objective response rate (ORR), duration of response (DoR) and progression-free survival (PFS) by RECIST 1.1. The CNS full analysis set (cFAS) comprised pts with ≥1 measurable and/or non-measurable CNS lesion present on baseline brain scan by BICR; the CNS evaluable for response set (cEFR) comprised pts with ≥1 measurable CNS lesion. Results: At the data cut-off of 4 November 2016, 59/171 pts (35%) were included in the cFAS. In the cFAS and cEFR (n = 23), 3 and 0 pts had brain radiotherapy ≤6 months prior to study entry, respectively. CNS ORR was 42% (25/59; 95% CI 30, 56) for the cFAS and 70% (16/23; 95% CI 47, 87) for the cEFR. Median CNS DoR was not reached (95% CI 9.2, not calculable [NC]) for the cFAS and 11.1 months (95% CI 8.2, NC) for the cEFR. CNS DCR was 85% (95% CI 73, 93) for the cFAS and 91% (95% CI 72, 99) for the cEFR. Median CNS PFS was not reached in both cFAS (95% CI 12.4, NC) and cEFR groups (95% CI 9.4, NC), with a median follow-up for CNS PFS of 7.1 and 8.2 months, respectively. At 12 months, 70% (95% CI 53, 82) of pts in the cFAS and 61% (95% CI 31, 81) of pts in the cEFR were estimated to remain on study, alive and CNS progression-free. Conclusions: These data are consistent with previous reports of CNS response to osimertinib in pts with T790M-positive advanced NSCLC in global studies, and demonstrate clinically meaningful efficacy in Asian-Pacific pts with CNS mets. Clinical trial identification: NCT02442349 Legal entity responsible for the study: AstraZeneca Funding: AstraZeneca Disclosure: C. Zhou: Lecture honorarium: Eli Lily, AZ, Roche, Pfizer, Sanofi, BI, Henrui Advisory board: Roche, BI, AZ. Y. Lu: Consulting or Advisory Role: AstraZeneca, Hoffmann-La Roche, Eli Lilly, Pfizer, Elekta, Varian Medical Systems. J. Wang, Y. Chen: Employee of AstraZeneca. Y-L. Wu: Speaker fees from AstraZeneca, Roche, Eli Lilly, Sanofi, Pfizer. All other authors have declared no conflicts of interest.

1354P - Osimertinib in Asia-Pacific patients (pts) with EGFR T790M-positive advanced NSCLC: Updated Phase II study results including progression-free survival (PFS)

1354P - Osimertinib in Asia-Pacific patients (pts) with EGFR T790M-positive advanced NSCLC: Updated Phase II study results including progression-free survival (PFS)

Osimertinib: A Review in T790M-Positive Advanced Non-Small Cell Lung Cancer.

Osimertinib (Tagrisso™) is an oral, CNS-active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets EGFR TKI-sensitizing mutations and, crucially, the T790M mutation that often underlies acquired resistance to EGFR TKI therapy. Osimertinib has been approved in numerous countries for use in patients with T790M-positive advanced NSCLC. In the pivotal, international AURA3 trial in patients with T790M-positive advanced NSCLC who had disease progression after EGFR TKI therapy, osimertinib treatment significantly prolonged progression-free survival (PFS; primary endpoint) compared with platinum-pemetrexed therapy at the time of the primary analysis. PFS results were consistent across predefined subgroups of patients, including those with CNS metastases at baseline. There was no difference between treatment groups in overall survival at 26% maturity. Objective response rates (ORRs) and patient-reported outcomes for prespecified symptoms were also significantly improved with osimertinib relative to platinum-pemetrexed, with CNS ORRs in patients with CNS metastases more than twofold higher in the osimertinib than in the platinum-pemetrexed group. Osimertinib had a manageable tolerability profile, with relatively few patients permanently discontinuing treatment because of adverse events (AEs). With limited treatment options available in this setting, osimertinib is an important option in adult patients with advanced EGFR T790M-positive NSCLC.

CNS response to osimertinib in patients (pts) with T790M-positive advanced NSCLC: Data from a randomized phase III trial (AURA3).

9005 Background: CNS metastases (mets) are common in pts with advanced NSCLC. Preclinical studies have shown CNS penetration of osimertinib, and clinical data from a pooled analysis of 2 Phase II trials (AURA extension: NCT01802632, AURA2: NCT02094261) showed activity in the CNS. We report the first evidence of osimertinib efficacy in CNS mets from a randomized Phase III study (AURA3; NCT02151981) in pts with T790M-positive advanced NSCLC who have progressed on or after prior EGFR-TKI therapy. Methods: Pts were randomized 2:1 to osimertinib 80 mg once daily or platinum-based doublet chemotherapy every 3 wks for up to 6 cycles; maintenance pemetrexed was allowed. Pts with stable, asymptomatic CNS mets were eligible for enrolment. A prespecified subgroup analysis was conducted in pts with CNS mets present on baseline brain scan, as assessed by blinded independent central neuroradiology review (BICR), to define CNS objective response rate (ORR), duration of response (DoR) and progression-free survival (PFS) by RECIST v1.1. The CNS full analysis set (cFAS) included pts with ≥1 measurable and/or non-measurable CNS mets present on baseline brain scan by BICR; the CNS evaluable for response set (cEFR) included only pts with ≥1 measurable CNS mets. Results: As of 15 April 2016, 116/419 (28%) pts were included in the cFAS. In the cEFR (n = 46), CNS ORR was 70% (21/30; 95% CI 51, 85) with osimertinib and 31% (5/16; 95% CI 11, 59) with chemotherapy (OR, 5.13; 95% CI 1.44, 20.64; p = 0.015). In the cFAS, CNS ORR was 40% (30/75; 95% CI 29, 52) with osimertinib and 17% (7/41; 95% CI 7, 32) with chemotherapy (OR, 3.24; 95% CI 1.33, 8.81; p = 0.014). In the cEFR and cFAS, median CNS DoR was 8.9 months (m) (95% CI 4.3, NC and 4.3, NC) for osimertinib and 5.7 m (95% CI NC, NC and 4.4, 5.7; respectively) for chemotherapy. Median CNS PFS in the cFAS was significantly longer with osimertinib than with chemotherapy (11.7 vs 5.6 m; HR 0.32; 95% CI 0.15, 0.69; p = 0.004). Conclusions: Consistent with the overall response to osimertinib reported in pts with T790M-positive advanced NSCLC, osimertinib was superior to chemotherapy in the treatment of pts with CNS mets; CNS response rate was higher, responses were more durable and CNS PFS was longer. Clinical trial information: NCT02151981.

Complete clearance of plasma EGFR mutations as a predictor of outcome on osimertinib in the AURA trial.

9018 Background: Osimertinib, an EGFR T790M-selective tyrosine kinase inhibitor (TKI), provides high and durable response rates in patients (pts) with T790M positive advanced NSCLC whose disease has progressed following EGFR-TKI therapy. We investigated whether changes in the levels of plasma EGFRmutations post-osimertinib treatment are associated with clinical outcome. Methods: We studied pts from the AURA Phase I study (NCT01802632) with acquired resistance to EGFR-TKIs, T790M positive baseline genotyping (in tumor or plasma), and plasma samples collected at baseline and 6 weeks (wks) post- osimertinib (20–240 mg daily) treatment. Plasma samples were analyzed for the presence of detectable EGFR mutations (Ex19del, L858R and T790M) using BEAMing digital PCR (Sysmex/Inostics). In pts with detectable plasma EGFR mutations at baseline, clinical outcomes (by investigator, per RECIST 1.1) were compared for pts with or without detectable plasma EGFRmutations at 6 wks. Results: Evaluable baseline and 6 wk plasma samples were collected from 160 pts with T790M positive genotyping, of whom 143 had detectable EGFR mutations at baseline (median allelic fraction for Ex19del: 7.09%; L858R: 3.81%; T790M: 2.12%). In this cohort, the overall median progression-free survival (mPFS) was 9.3 months (m; 95% CI 8.2, 9.7). Clearance of plasma EGFRmutations at 6 wks was seen in 92/143 (64%) pts. mPFS was longer in pts with plasma clearance (10.9 m; 95% CI 9.5, 15.2) compared with pts without (5.5 m; 95% CI 3.9, 6.7), as was objective response rate (ORR; 70%; 95% CI 59%, 79% vs. 35%; 95% CI 22%, 50%). Conclusions: Clearance of plasma EGFR mutations after 6 wks of osimertinib therapy appears to be associated with improved ORR and mPFS in pts with T790M positive NSCLC. Evidence or lack of such a “plasma response” measured at 6 wks could, potentially, be used to predict subsequent outcomes on therapy. Further research is needed to better understand whether continued detection of plasma EGFR mutations at 6 wks may indicate the presence of heterogeneous resistance mechanisms, which could, potentially, be targeted by combination therapies. Validation of these results in an independent cohort of pts is ongoing. Clinical trial information: NCT02228369.

MA16.11 CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC: Pooled Data from Two Phase II Trials

MA16.11 CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC: Pooled Data from Two Phase II Trials

PL03.03: Randomized Phase III Study of Osimertinib vs Platinum-Pemetrexed for EGFR T790M-Positive Advanced NSCLC (AURA3)

Osimertinib is a potent, irreversible, CNS active, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for sensitizing (EGFRm) and T790M resistance mutations. Osimertinib is indicated for the treatment of patients with locally advanced or metastatic EGFR T790M-positive NSCLC. AURA3 (NCT02151981) is a Phase III, open-label, randomized study assessing the efficacy and safety of osimertinib versus platinum-based chemotherapy plus pemetrexed in patients with EGFR T790M-positive advanced NSCLC, whose tumors progressed on first-line EGFR-TKI therapy. Eligible patients were ≥18 years with documented EGFRm, radiological disease progression following first-line EGFR-TKI and centrally confirmed T790M-positive (by cobas® EGFR Mutation Test) from a tissue biopsy after disease progression. Asymptomatic, stable CNS metastases were allowed. Patients were randomized 2:1 to osimertinib 80 mg orally, once daily or platinum-pemetrexed (pemetrexed 500 mg/m2 plus either cisplatin 75 mg/m2 or carboplatin AUC5) every three weeks for up to six cycles; pemetrexed could be continued as maintenance treatment. Primary endpoint was progression-free survival (PFS) by investigator assessment according to RECIST v1.1; sensitivity analysis was by blinded independent central review (BICR). A total of 419 patients were randomized to treatment (osimertinib, n=279; platinum-pemetrexed, n=140). Baseline characteristics were generally balanced across treatment groups: female 64%, Asian 65%, never smoker 68%, CNS metastases 34%, EGFR exon 19 deletion 66%. Osimertinib significantly improved PFS compared with platinum-pemetrexed: hazard ratio [HR] 0.30; 95% CI: 0.23, 0.41; p<0.001 (median 10.1 months vs 4.4 months). The result was consistent with PFS analysis by BICR: HR 0.28; 95% CI: 0.20, 0.38; p<0.001 (11.0 months vs 4.2 months). Objective response rate was significantly improved with osimertinib (71%) vs platinum-pemetrexed (31%); odds ratio 5.39 (95% CI: 3.47, 8.48; p<0.001). Median duration of response was 9.7 months (95% CI 8.3, 11.6) with osimertinib and 4.1 months (95% CI 3.0, 5.6) with platinum-pemetrexed. Grade ≥3 causally-related adverse events (AEs) as assessed by the investigator were reported in 6% of patients (n=16) treated with osimertinib and 34% (n=46) treated with platinum-pemetrexed. Most common causally-related AEs in the osimertinib group: diarrhoea (29% [grade ≥3, 1%]), rash (28% [<1%]); in the platinum-pemetrexed group: nausea (47% [3%]), decreased appetite (32% [3%]). In patients with EGFR T790M-positive advanced NSCLC following progression on EGFR-TKI treatment, osimertinib demonstrated a superior clinically-meaningful efficacy over platinum-pemetrexed, with a 70% reduction in the risk of disease progression, and well-characterized safety profile, establishing the new standard of care for these patients.

LBA1_PR: Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two Phase I expansion cohorts

LBA1_PR: Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two Phase I expansion cohorts

LBA2_PR: Osimertinib (AZD9291) in pre-treated pts with T790M-positive advanced NSCLC: updated Phase 1 (P1) and pooled Phase 2 (P2) results

LBA2_PR: Osimertinib (AZD9291) in pre-treated pts with T790M-positive advanced NSCLC: updated Phase 1 (P1) and pooled Phase 2 (P2) results