Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

ePoster Display

1239P - ORCHARD osimertinib + savolitinib interim analysis: A biomarker-directed phase II platform study in patients (pts) with advanced non-small cell lung cancer (NSCLC) whose disease has progressed on first-line (1L) osimertinib

Date

16 Sep 2021

Session

ePoster Display

Presenters

Helena A. Yu

Citation

Annals of Oncology (2021) 32 (suppl_5): S949-S1039. 10.1016/annonc/annonc729

Authors

H.A. Yu1, H. Ambrose2, C. Baik3, B.C. Cho4, E. Cocco5, S.B. Goldberg6, J.W. Goldman7, S. Kraljevic2, A.J. de Langen8, I. Okamoto9, Z. Piotrowska10, M. Pluta11, S. Powar12, N. Reguart Aransay13, J.W. Riess14, X. Le15

Author affiliations

  • 1 Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 10065 - New York/US
  • 2 Early Oncology, Oncology R&d, AstraZeneca, Cambridge/GB
  • 3 Department Of Medicine, Division Of Medical Oncology, University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle/US
  • 4 Division Of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/KR
  • 5 Translational Medicine, Oncology R&d, AstraZeneca, Boston/US
  • 6 Department Of Medicine (medical Oncology), Yale University School of Medicine - Yale Cancer Center, 06520 - New Haven/US
  • 7 Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles/US
  • 8 Department Of Thoracic Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam/NL
  • 9 Research Institute For Diseases Of The Chest, Graduate School of Medical Sciences, Kyushu University, 82 - Fukuoka/JP
  • 10 Department Of Medicine, Massachusetts General Hospital, Boston/US
  • 11 Early Oncology, Oncology Statistics, AstraZeneca, Cambridge/GB
  • 12 Clinical Research, Global Patient Safety, AstraZeneca, Cambridge/GB
  • 13 Department Of Medical Oncology, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic de Barcelona, Barcelona/ES
  • 14 Internal Medicine – Hematology/oncology, University California Davis Comprehensive Cancer Center, Sacramento/US
  • 15 Department Of Thoracic/head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
More

Abstract 1239P

Background

Most pts with epidermal growth factor receptor mutation-positive (EGFRm) NSCLC treated with osimertinib, a third-generation, irreversible, CNS-active EGFR-tyrosine kinase inhibitor (TKI), eventually develop resistance. MET alterations are common resistance mechanisms to osimertinib. The phase II ORCHARD platform study (NCT03944772) aims to characterise 1L osimertinib resistance mechanisms and identify optimal post-progression therapies. This interim analysis reports use of osimertinib + savolitinib, an oral, potent and highly selective MET-TKI, in adults with EGFRm advanced NSCLC and MET alterations (MET amplification / MET exon 14 skipping).

Methods

Pts were allocated to treatment cohorts after disease progression on 1L osimertinib, based on molecular profiling of a tumour biopsy with NGS. Pts whose tumours harbour MET alterations were allocated to osimertinib 80 mg qd + savolitinib 300 or 600 mg qd. Primary endpoint: investigator assessed objective response rate (ORR; RECIST v1.1). Other endpoints include duration of response and safety / tolerability. Interim data cut-off (DCO): Jan 2021.

Results

Of 20 pts that received osimertinib + savolitinib, median duration on prior 1L osimertinib was 414 (197–1722) days. At DCO, 17 pts were evaluable for confirmed response. ORR was 41% (n=7; 80% CI: 25, 59); 7 pts (41%) had partial response, 7 (41%) had stable disease and 1 (6%) had disease progression as their best response; 2 pts (12%) were not evaluable. Overall, 6 / 20 pts (30%) reported a grade ≥3 adverse event (AE), most commonly pneumonia and decreased neutrophil count (each n=2; 10%); 6 / 20 pts (30%) reported a serious AE. Three pts (15%) discontinued combination treatment due to AEs. No deaths due to AEs were reported.

Conclusions

Osimertinib + savolitinib showed preliminary activity in pts with MET alterations after 1L osimertinib. Based on interim efficacy, enrolment will continue to 30 pts as pre-specified per protocol. The safety profile was acceptable and consistent with known profiles of osimertinib / savolitinib. Further exploration of this combination is underway in the SAVANNAH study (NCT03778229).

Clinical trial identification

NCT03944772.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Gemma White, MSc, of Ashfield MedComms, an Ashfield Health company, and funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

H.A. Yu: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: Cullinan; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Research Grant: Daiichi Sankyo. H. Ambrose: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. C. Baik: Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Loxo Oncology; Financial Interests, Personal and Institutional, Research Grant: Genentech Inc.; Financial Interests, Personal and Institutional, Research Grant: Spectrum Pharmaceuticals; Financial Interests, Personal and Institutional, Research Grant: Blueprint Medicines; Financial Interests, Personal and Institutional, Research Grant: Daiichi Sankyo Inc.; Financial Interests, Personal and Institutional, Research Grant: Rain Therapeutics; Financial Interests, Personal and Institutional, Research Grant: AbbVie; Financial Interests, Personal and Institutional, Research Grant: Turning Point Therapeutics; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: Janssen; Financial Interests, Personal, Advisory Role, Consulting Fees: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting Fees: Blueprint Medicines; Financial Interests, Personal, Advisory Role, Consulting Fees: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consulting Fees: Takeda; Financial Interests, Personal, Advisory Role, Consulting Fees: Turning Point Therapeutics. B.C. Cho: Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc.; Financial Interests, Personal, Advisory Board: BridgeBio Therapeutics; Financial Interests, Personal, Advisory Board: Cyrus Therapeutics; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Mogam Institute; Financial Interests, Personal and Institutional, Research Grant: Dong-A ST; Financial Interests, Personal and Institutional, Research Grant: Champions Oncology; Financial Interests, Personal and Institutional, Research Grant: Janssen; Financial Interests, Personal and Institutional, Research Grant: Yuhan; Financial Interests, Personal and Institutional, Research Grant: Ono Pharmaceuticals; Financial Interests, Personal and Institutional, Research Grant: Dizal Pharma; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Research Grant: AbbVie; Financial Interests, Personal and Institutional, Research Grant: Medpacto; Financial Interests, Personal and Institutional, Research Grant: GI Innovation; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: Blueprint Medicines; Financial Interests, Personal and Institutional, Research Grant: Interpark Bio Convergence Corp; Financial Interests, Personal, Advisory Role, Consulting fees: Novartis; Financial Interests, Personal, Advisory Role, Consulting fees: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting fees: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role, Consulting fees: Roche; Financial Interests, Personal, Advisory Role, Consulting fees: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting fees: Ono Pharmaceuticals; Financial Interests, Personal, Advisory Role, Consulting fees: Yuhan; Financial Interests, Personal, Advisory Role, Consulting fees: Pfizer; Financial Interests, Personal, Advisory Role, Consulting fees: Eli Lilly; Financial Interests, Personal, Advisory Role, Consulting fees: Janssen; Financial Interests, Personal, Advisory Role, Consulting fees: Takeda; Financial Interests, Personal, Advisory Role, Consulting fees: MSD; Financial Interests, Personal, Advisory Role, Consulting fees: Medpacto; Financial Interests, Personal, Advisory Role, Consulting fees: Blueprint Medicines; Financial Interests, Personal, Ownership Interest, Founder: DAAN Biotherapeutics. E. Cocco: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S.B. Goldberg: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Spectrum; Financial Interests, Personal, Advisory Board: Blueprint Medicine; Financial Interests, Personal, Advisory Board: Sanofi Genzyme; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Boehringer Ingelheim. J.W. Goldman: Financial Interests, Personal and Institutional, Research Grant: Advaxis; Financial Interests, Personal and Institutional, Research Grant: Array Biopharma; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: Genentech/Roche; Financial Interests, Personal and Institutional, Research Grant: G1 Therapeutics; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal and Institutional, Research Grant: Pfizer Inc.; Financial Interests, Personal, Other, Travel: AstraZeneca. S. Kraljevic: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A.J. de Langen: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: MSD. I. Okamoto: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Chugai Pharma; Financial Interests, Personal, Other, Grants/patents received or pending: Pfizer Inc.; Financial Interests, Personal, Other, Grants/patents received or pending: Boehringer Ingelheim; Financial Interests, Personal, Other, Grants/patents received or pending: Taiho Pharmaceutical; Financial Interests, Personal, Other, Grants/patents received or pending: Ono Pharmaceutical; Financial Interests, Personal, Other, Grants/patents received or pending: MSD Oncology; Financial Interests, Personal, Other, Grants/patents received or pending: Astellas Pharma; Financial Interests, Personal, Other, Grants/patents received or pending: Bristol Myers Squibb; Financial Interests, Personal, Officer, Grants/patents received or pending: Chugai Pharma; Financial Interests, Personal, Officer, Grants/patents received or pending: AbbVie. Z. Piotrowska: Financial Interests, Personal, Advisory Role, Consultancy fees: AstraZeneca; Financial Interests, Personal, Advisory Role, Consultancy fees: Blueprint Medicines; Financial Interests, Personal, Advisory Role, Consultancy fees: Janssen; Financial Interests, Personal, Advisory Role, Consultancy fees: Takeda; Financial Interests, Personal, Advisory Role, Consultancy fees: Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Role, Consultancy fees: C4 Therapeutics; Financial Interests, Personal, Other, Grants/patents received or pending: Novartis; Financial Interests, Personal, Other, Grants/patents received or pending: Takeda; Financial Interests, Personal, Other, Grants/patents received or pending: Spectrum Pharmaceuticals; Financial Interests, Personal, Other, Grants/patents received or pending: AstraZeneca; Financial Interests, Personal, Other, Grants/patents received or pending: Tesaro; Financial Interests, Personal, Other, Grants/patents received or pending: Cullinan; Financial Interests, Personal, Other, Grants/patents received or pending: Daiichi Sankyo; Financial Interests, Personal, Other, Grants/patents received or pending: AbbVie. M. Pluta: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Powar: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. N. Reguart Aransay: Financial Interests, Personal, Advisory Board: Pfizer Inc.; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: MSI; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Guardant Health; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Sanofi. J.W. Riess: Financial Interests, Personal, Other, Honoraria: Blueprint Medicine; Financial Interests, Personal, Other, Honoraria: EcoRI; Financial Interests, Personal, Other, Honoraria: Medtronic; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: EMD Serrano; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Advisory Role, Consultancy fees: Novartis; Financial Interests, Personal, Advisory Role, Consultancy fees: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role, Consultancy fees: Genentech; Financial Interests, Personal, Advisory Role, Consultancy fees: Blueprint Medicine. X. Le: Financial Interests, Personal, Advisory Role, Consultancy fees: EMD Serono (Merck KGaA); Financial Interests, Personal, Advisory Role, Consultancy fees: AstraZeneca; Financial Interests, Personal, Advisory Role, Consultancy fees: Spectrum Pharmaceutics; Financial Interests, Personal, Advisory Role, Consultancy fees: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consultancy fees: Eli Lilly; Financial Interests, Personal, Funding, Research grant pending: Eli Lilly; Financial Interests, Personal, Funding, Research grant pending: Eli Lilly.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings