TY - JOUR
T1 - Biomarker-Directed Phase II Platform Study in Patients With EGFR Sensitizing Mutation-Positive Advanced/Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy (ORCHARD)
AU - Yu, Helena A.
AU - Goldberg, Sarah B.
AU - Le, Xiuning
AU - Piotrowska, Zofia
AU - Goldman, Jonathan W.
AU - De Langen, Adrianus J.
AU - Okamoto, Isamu
AU - Cho, Byoung Chul
AU - Smith, Paul
AU - Mensi, Ilhem
AU - Ambrose, Helen
AU - Kraljevic, Silvija
AU - Maidment, Julie
AU - Chmielecki, Juliann
AU - Li-Sucholeiki, Xiaocheng
AU - Doughton, Gail
AU - Patel, Gargi
AU - Jewsbury, Phil
AU - Szekeres, Phil
AU - Riess, Jonathan W.
N1 - Funding Information:
The authors would like to thank the ORCHARD study team, the site staff and the patients involved in this study. The study (NCT03944772) was funded by AstraZeneca , Cambridge, United Kingdom, the manufacturer of osimertinib, savolitinib, durvalumab and gefitinib. The authors would like to acknowledge Eli Lilly and Company, the manufacturer of necitumumab and selpercatinib, and Roche, the manufacturer of alectinib. The authors would like to acknowledge Eleanor Thomas, BSc, and Alexandra Webster, MSc, of Ashfield MedComms, part of Ashfield Health for medical writing support that was funded by AstraZeneca, Cambridge, UK in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
Funding Information:
The authors would like to thank the ORCHARD study team, the site staff and the patients involved in this study. The study (NCT03944772) was funded by AstraZeneca, Cambridge, United Kingdom, the manufacturer of osimertinib, savolitinib, durvalumab and gefitinib. The authors would like to acknowledge Eli Lilly and Company, the manufacturer of necitumumab and selpercatinib, and Roche, the manufacturer of alectinib. The authors would like to acknowledge Eleanor Thomas, BSc, and Alexandra Webster, MSc, of Ashfield MedComms, part of Ashfield Health for medical writing support that was funded by AstraZeneca, Cambridge, UK in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/11
Y1 - 2021/11
N2 - Introduction: Osimertinib, a third-generation, irreversible, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), selectively inhibits both EGFR-TKI sensitizing (EGFRm) and EGFR T790M resistance mutations and has demonstrated efficacy in non-small cell lung cancer (NSCLC) CNS metastases. Most patients with EGFRm NSCLC treated with osimertinib will eventually develop resistance. ORCHARD (NCT03944772) is a phase II study aiming to characterize first-line osimertinib resistance and identify post-progression treatments. Methods: Adults aged ≥ 18 years (Japan ≥ 20 years), with EGFRm locally advanced/metastatic NSCLC will be allocated to one of three groups after first-line osimertinib progression, based on molecular profiling from a post-progression tumor biopsy. Group A will evaluate patients with protocol-determined biomarkers of resistance treated with novel osimertinib combination therapies, Group B will evaluate patients without a detectable protocol-determined biomarker treated with non-biomarker selected therapies that are chemotherapy- or EGFR-TKI-based, and Group C (observational) includes patients with histologically transformed disease, and/or a biomarker with an available therapy not investigated in ORCHARD. Group C patients will be treated as per local practice and followed to assess overall survival. The study's platform design allows for adaptability to include emerging treatments related to novel resistance mechanisms. The primary endpoint is confirmed objective response rate (investigator assessed). Other endpoints are progression-free survival, duration of response, overall survival, pharmacokinetics and safety. Conclusions: ORCHARD aims to characterize mechanisms of resistance to first-line osimertinib and explore treatments to overcome acquired resistance. The modular design allows for additional biomarker-directed cohorts and treatment options as understanding of osimertinib resistance mechanisms evolves.
AB - Introduction: Osimertinib, a third-generation, irreversible, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), selectively inhibits both EGFR-TKI sensitizing (EGFRm) and EGFR T790M resistance mutations and has demonstrated efficacy in non-small cell lung cancer (NSCLC) CNS metastases. Most patients with EGFRm NSCLC treated with osimertinib will eventually develop resistance. ORCHARD (NCT03944772) is a phase II study aiming to characterize first-line osimertinib resistance and identify post-progression treatments. Methods: Adults aged ≥ 18 years (Japan ≥ 20 years), with EGFRm locally advanced/metastatic NSCLC will be allocated to one of three groups after first-line osimertinib progression, based on molecular profiling from a post-progression tumor biopsy. Group A will evaluate patients with protocol-determined biomarkers of resistance treated with novel osimertinib combination therapies, Group B will evaluate patients without a detectable protocol-determined biomarker treated with non-biomarker selected therapies that are chemotherapy- or EGFR-TKI-based, and Group C (observational) includes patients with histologically transformed disease, and/or a biomarker with an available therapy not investigated in ORCHARD. Group C patients will be treated as per local practice and followed to assess overall survival. The study's platform design allows for adaptability to include emerging treatments related to novel resistance mechanisms. The primary endpoint is confirmed objective response rate (investigator assessed). Other endpoints are progression-free survival, duration of response, overall survival, pharmacokinetics and safety. Conclusions: ORCHARD aims to characterize mechanisms of resistance to first-line osimertinib and explore treatments to overcome acquired resistance. The modular design allows for additional biomarker-directed cohorts and treatment options as understanding of osimertinib resistance mechanisms evolves.
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U2 - 10.1016/j.cllc.2021.06.006
DO - 10.1016/j.cllc.2021.06.006
M3 - Article
C2 - 34389237
AN - SCOPUS:85112546892
SN - 1525-7304
VL - 22
SP - 601
EP - 606
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 6
ER -
