1205MO - Updated analysis of DESTINY-Gastric02: A phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable/metastatic gastric/gastroesophageal junction (GEJ) cancer who progressed on or after trastuzumab-containing regimen

Background

Primary results of DESTINY-Gastric02 (NCT04014075; data cutoff [DCO] April 9, 2021), a single-arm, phase II trial of T-DXd in Western pts with HER2+ gastric/GEJ cancer, demonstrated a confirmed objective response rate (cORR) of 38.0% (95% CI, 27.3-49.6), and safety consistent with the established T-DXd safety profile. We report OS and updated efficacy and safety.

Methods

Pts with centrally confirmed HER2+ (IHC3+ or IHC2+/ISH+ biopsy after progression on trastuzumab-based therapy) unresectable/metastatic gastric/GEJ cancer who progressed on or after 1L therapy received T-DXd 6.4 mg/kg Q3W. The primary endpoint was cORR per RECIST v1.1 by independent central review (ICR). Progression-free survival (PFS) by ICR, duration of response (DOR) by ICR, OS, and patient-reported outcomes based on the European Organization for Research and Treatment of Cancer 5-dimension 5-levels (EQ-5D-5L) quality-of-life (QoL) and Functional Assessment of Cancer Therapy-Gastric (FACT-GA) questionnaires were secondary endpoints.

Results

At DCO (November 8, 2021), 79 pts from the US/EU had received T-DXd. 76 pts (96.2%) had received 1 prior line of therapy and 3 (3.8%) had received 2 lines. With a median duration of follow up of 10.2 mo, 10 pts (12.7%) remained on treatment. Median OS was 12.1 mo (95% CI, 9.4-15.4); landmark 12-mo OS rate was 50.6%. cORR was 41.8% (33/79; 4 complete and 29 partial responses). Median DOR was 8.1 mo (95% CI, 5.9-NE). Median PFS was 5.6 mo (95% CI, 4.2-8.3). All pts experienced ≥1 treatment-emergent adverse event (TEAE); 55.7% experienced grade ≥3 TEAEs. The most common TEAEs were nausea (67.1%), vomiting (44.3%) and fatigue (57.0%). Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8 pts (10.1%); 6 (7.6%) had grade 1-2 and 2 (2.5%) had grade 5. At DCO (April 9, 2021), QoL assessed by EQ-5D-5L and FACT-GA had been maintained over the treatment course.

Conclusions

T-DXd continues to demonstrate substantial clinical benefit and a tolerable safety profile in 2L+ Western pts with HER2+ unresectable/metastatic gastric/GEJ cancer.

Clinical trial identification

NCT04014075.

Editorial acknowledgement

Under the guidance of authors, medical writing and editorial support was provided by Marianna Johnson, PhD, Rachel Hood, PhD, and Laura Halvorson, PhD of ApotheCom and was funded by Daiichi Sankyo.

Legal entity responsible for the study

Daiichi Sankyo and AstraZeneca.

Funding

Daiichi Sankyo and AstraZeneca.

Disclosure

G.Y. Ku: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, IMAB, Merck, Pieris, Zymeworks; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, CARSgen, IMAB, Merck, Pieris, Zymeworks. M. Di Bartolomeo: Financial Interests, Personal, Advisory Board, Consultant: Lilly; Financial Interests, Personal, Advisory Board, consultant: Novartis, AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Institutional, Other, Research founding: Lilly spa; Financial Interests, Institutional, Invited Speaker: MSD, BMS, AstraZeneca, Daiichi, Incyte. E. Smyth: Financial Interests, Personal, Invited Speaker: Amgen, Bristol-Myers Squibb, Imedex, Merck, Novartis, Prova Education, Servier, TouchIME; Financial Interests, Personal, Other, TSC: Amgen; Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bristol-Myers Squibb, My Personal Therapeutics, Novartis, Roche, Servier, Zymeworks; Financial Interests, Personal, Other, IDMC: Beigene, Zymeworks; Financial Interests, Personal, Expert Testimony: Bristol-Myers Squibb; Financial Interests, Personal, Other, IDMC chair: Everest Clinical Research; Financial Interests, Personal, Officer: EORTC GI Clinical Trials Group; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Roche, AstraZeneca, Merus, Basilea, MSD; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb. I. Chau: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eli-Lilly, MSD, Roche, Merck Serono, AstraZeneca, OncXerna, Pierre Fabre, Boehinger Ingelheim, Astella, Incyte, GSK, Sotio, Daiichi-Sankyo, Eisai; Financial Interests, Personal, Other, DMC chairman: Five Prime Therapeutics; Financial Interests, Personal, Invited Speaker: Eisai, Eli-Lilly, Servier; Financial Interests, Institutional, Invited Speaker: Cilag-Janssen, Eli Lilly. H. Park: Financial Interests, Institutional, Research Grant: Adlai Nortye USA, Alpine Immune Sciences, Ambryx, Amgen, Aprea Therapeutics AB, Array BioPharma, Bayer, BeiGene, BJ Bioscience, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Elicio Therapeutics, EMD Serono, Exelixis, Genentech, Gilead Sciences, GlaxoSmithKline, Grossamer Bio, Hoffman-LaRoche, Hutchison, MediPharma, ImmuneOncia Therapeutics, Incyte, Jounce Therapeutics, Mabspace Biosciences, MacroGenics, Medimmune, Medivation, MERCK, Milennium, Mirati Therapeutics, Novartis, Oncologie, Pfizer, PsiOxus Therapeutics, Puma Biotechnology, Regeneron, RePare Therapeutics, Seattle Genetics, Synermore Biologics, Taiho Pharmaceutical, TopAlliance Biosciences, Turning Point Therapeutics, Vedanta Biosciences, Xencore Inc. S. Siena: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Bayer, BMS, CheckmAb, Daiichi-Sankyo, Guardant Health, Menarini, Merck, Novartis, Roche-Genentech, Seagen. S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi-Sankyo, Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, GlaxoSmithKline; Financial Interests, Institutional, Invited Speaker: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol -Myers Squibb. Z.A. Wainberg: Financial Interests, Personal, Other, Honoraria: Amgen, Astra Zenica, Daiichi Sankyo, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas, Molecular Templates, Array; Financial Interests, Personal, Advisory Board: Amgen, Astrazenica, Daiichi Sankyo, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas, Molecular Templates, Array; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Daiichi Sanyko, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas, Molecular Templates, Roche/Genentech, Array/Pfizer. J.A. Ajani: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, AstraZenica; Financial Interests, Institutional, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Other, Travel Expenses: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Daiichi Sankyo. J. Chao: Financial Interests, Personal, Advisory Board: Merck, Amgen, Daiichi Sankyo, Macrogenics, Bristol Myers Squibb, Astellas, Turning Point Therapeutics; Financial Interests, Personal, Invited Speaker: Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting: Lilly, AstraZeneca, Ono Pharmaceuticals, Roche; Financial Interests, Institutional, Funding: Merck, Brooklyn Immunotherapeutics. F. Barlaskar: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Kawaguchi: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. A. Qin: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Singh: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. G. Meinhardt: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Bayer Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. E. Van Cutsem: Financial Interests, Personal, Advisory Board, Advisory board and/or Speaking: AbbVie, Array, Astellas, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabr; Financial Interests, Institutional, Funding, research grant paid to institution: Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier.