Abstract 13P
Background
Osimertinib is third generation, irreversible, CNS-active EGFR-TKI, and preferred 1L treatment in pts with advanced EGFRm NSCLC. Pts on 1L osimertinib may develop treatment resistance and experience disease progression. The ongoing phase II, open-label, biomarker-directed platform study ORCHARD (NCT03944772) aims to characterise resistance mechanisms and evaluate novel therapy combinations in pts who progressed on 1L osimertinib. This interim analysis reports results of durvalumab + chemotherapy in pts with no biomarker-detected resistance mechanisms or for whom biomarker-directed study treatments were not available.
Methods
Adults (WHO PS 0–1) with EGFRm NSCLC who did not harbour a pre-specified alteration by next-generation sequencing on post-TKI biopsy, received durvalumab (1500 mg; intravenous, IV) + carboplatin (target area under the curve 5; IV) + pemetrexed (500 mg/m2 body surface area; IV) on Day 1 of 21-day cycles for 4–6 cycles, followed by durvalumab + pemetrexed maintenance treatment on Day 1 of 28-day cycles, thereafter. Primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. Data cut-off (DCO): 25 June 2021.
Results
Twenty-five pts (median age, 61 yrs; female, n=19 [76%]; CNS metastases, n=6 [24%]) were enrolled. All pts received ≥75% relative dose intensity for all study drugs; 22 pts (88%) discontinued all treatments by DCO. ORR was 12% (n=3/25; confidence intervals, CI: 4, 25; confirmed partial responses). Stable disease was reported in 17/25 pts (68%; including six unconfirmed partial responses [24%]) and progressive disease in 4/25 (16%) pts. One (4%) pt was non-evaluable. Median PFS was 4.8 months (95% CI: 2.6, 7.6). Recruitment was paused as stop criteria (≤10% chance ORR is ≥45%) were met. Treatment-related serious adverse events occurred in two pts (8%); there were no interstitial lung disease events.
Conclusions
In this pt population, durvalumab + chemotherapy treatment was well tolerated with no new safety signals; however, stop criteria were met with this combination, and recruitment was closed.
Clinical trial identification
NCT03944772.
Editorial acknowledgement
Leon Newman, PhD, of Ashfield MedComms, provided medical writing support that was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
B.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc; Financial Interests, Personal, Advisory Board: Brigebio therapeutics; Financial Interests, Personal, Advisory Board: Cyrus therapeutics; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Joseah BIO; Financial Interests, Personal, Member of the Board of Directors: Gencurix Inc; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp; Financial Interests, Personal, Ownership Interest: DAAN Biotherapeutics; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc; Financial Interests, Personal, Stocks/Shares: Gencurix Inc; Financial Interests, Personal, Stocks/Shares: Bridgebio therapeutics; Financial Interests, Personal, Stocks/Shares: KANAPH Therapeutic Inc; Financial Interests, Personal, Stocks/Shares: Cyrus therapeutics; Financial Interests, Personal, Stocks/Shares: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: MOGAM Institute; Financial Interests, Personal, Research Grant: Dong-A ST; Financial Interests, Personal, Research Grant: Champions Oncology; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Research Grant: Yuhan; Financial Interests, Personal, Research Grant: Ono; Financial Interests, Personal, Research Grant: Dizal Pharma; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Research Grant: Medpacto; Financial Interests, Personal, Research Grant: Gllnnovation; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Blueprint medicines; Financial Interests, Personal, Research Grant: Interpark Bio Convergence Corp.; Financial Interests, Personal, Other, Consulting fees: Novartis; Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: Boehringer-Ingelheim, Roche; Financial Interests, Personal, Other, Consulting fees: Bristol Myers Squibb; Financial Interests, Personal, Other, consulting fees: Ono; Financial Interests, Personal, Other, consulting fees: Yuhan; Financial Interests, Personal, Other, consulting fees: Pfizer; Financial Interests, Personal, Other, consulting fees: Eli Lilly; Financial Interests, Personal, Other, consulting fees: Janssen; Financial Interests, Personal, Other, consulting fees: Takeda; Financial Interests, Personal, Other, consulting fees: MSD; Financial Interests, Personal, Other, consulting fees: Medpacto; Financial Interests, Personal, Other, consulting fees: Blueprint medicines. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Alpha Pharmaceutical. C. Baik: Financial Interests, Personal, Advisory Board: BluePrint; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: TurningPoint; Financial Interests, Personal, Advisory Board: Guardant; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Silverback; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Spectrum; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Blueprint; Financial Interests, Institutional, Research Grant: TurningPoint. R. García: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: BI; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: BI; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Janssen; Non-Financial Interests, Personal, Principal Investigator: MSD; Non-Financial Interests, Personal, Principal Investigator: Roche; Non-Financial Interests, Personal, Principal Investigator: Takeda; Non-Financial Interests, Personal, Principal Investigator: Lilly; Non-Financial Interests, Personal, Principal Investigator: Novartis; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: Pfizer; Non-Financial Interests, Personal, Principal Investigator: BI; Non-Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: Janssen; Non-Financial Interests, Personal, Principal Investigator: Verastem; Non-Financial Interests, Personal, Principal Investigator: Amgen; Non-Financial Interests, Personal, Advisory Role: MSD; Non-Financial Interests, Personal, Advisory Role: Roche; Non-Financial Interests, Personal, Advisory Role: Takeda; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: Pfizer; Non-Financial Interests, Personal, Advisory Role: BI; Non-Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Janssen. J.W. Goldman: Financial Interests, Personal, Research Grant: Advaxis; Financial Interests, Personal, Research Grant: Array; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Genentech/Roche; Financial Interests, Personal, Research Grant: G1 Therapeutics; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Other, Honoria: AstraZeneca; Financial Interests, Personal, Other, Honoria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoria: Genentech; Financial Interests, Personal, Other, Honoria: Pfizer. S. Kim: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Eli Lilly & Co; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Other: Boehringer-Ingelheim. M. Nishio: Financial Interests, Personal, Advisory Role, Consultancy fees, honoraria: Lilly; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Personal, Advisory Role, Consultancy fees, honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role, Consultancy fees, honoraria: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Advisory Role, consulting/advisory: AbbVie; Financial Interests, Personal, Advisory Role, consulting/advisory: Takeda; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Personal, Other, honoraria: Takeda; Financial Interests, Personal, Other, honoraria: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, Honoraria: Nippon Kayaku; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Personal, Advisory Role, consulting/advisory: Teijin Pharma. R. Salgia: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Advisory Board: Janssen. S. Teraoka: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Pfizer Inc. T. Yoshida: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: ONO Pharmaceutical; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical; Financial Interests, Personal, Research Grant: ONO Pharmaceutical; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: Chugai Pharmaceutical; Financial Interests, Personal, Principal Investigator: ONO Pharmaceutical. H.A. Yu: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Cullinan; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria: BluePrint Medicine; Financial Interests, Personal, Other, Honoraria: C4 Therapeutics; Financial Interests, Personal, Other, Honoraria: Daiichi. H. Ambrose: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Cosaert: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Project Lead, Lead MD on AZ-sponsored trials: AstraZeneca; Financial Interests, Personal, Leadership Role, Lead MD on AZ-sponsored trials: AstraZeneca. R. Hartmaier: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Maidment: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Pluta: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. I. Okamoto: Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Ono Pharmaceutical; Financial Interests, Personal, Research Grant: MSD Oncology; Financial Interests, Personal, Research Grant: Astellas Pharma; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Chugai Pharma; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Personal, Other, 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, Honoraria: Pfizer. All other authors have declared no conflicts of interest.