Abstract 84MO
Background
T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody and topoisomerase I inhibitor payload. Early studies have shown promising activity in advanced HER2-expressing tumors. DESTINY-CRC01 (NCT03384940) is a phase II, open-label, multicenter study of T-DXd in HER2-expressing mCRC.
Methods
Patients (pts) with centrally confirmed HER2-expressing, RAS-wild type mCRC that progressed on ≥ 2 prior regimens received T-DXd 6.4 mg/kg every 3 weeks (q3w) in 3 cohorts (A: HER2 IHC 3+ or IHC 2+/ISH+; B: IHC 2+/ISH−; C: IHC 1+). The primary endpoint was confirmed objective response rate (ORR) by independent central review in cohort A; secondary endpoints included, disease control rate (DCR; CR + PR + SD), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and ORR in cohorts B and C.
Results
At data cutoff (Aug 9, 2019), 78 pts (A, 53; B, 7; C, 18) had received T-DXd. Median age was 58.5 y, 52.6% of pts were male, and 89.7% had left colon or rectum cancer; median number of prior regimens was 4; all pts had prior irinotecan. Median treatment duration was 3.5 mo; 38.5% of pts remained on T-DXd treatment. The confirmed ORR was 45.3% (24/53 pts; 95% CI, 31.6-59.6%) in cohort A, including 1 CR and 23 PRs; median DOR was not reached. The ORR in pts with prior anti-HER2 treatment was 43.8% (7/16 pts; 95% CI, 19.8-70.1%). The DCR was 83.0% (44/53 pts; 95% CI, 70.2-91.9%); median PFS was 6.9 mo (95% CI, 4.1 mo-NE); median OS was not reached. No responses were observed in cohort B or C. Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 61.5% of 78 pts; the most common (≥10%) were neutrophil count decreased (21.8%) and anemia (14.1%). Seven pts (9.0%) had TEAEs leading to drug discontinuation. Five pts (6.4%) had interstitial lung disease (ILD) adjudicated by an independent committee as related to T-DXd (2 grade 2; 1 grade 3; 2 grade 5 [the only drug related deaths]).
Conclusions
T-DXd demonstrated remarkable activity in pts with HER2-expressing mCRC refractory to standard therapies, with a safety profile consistent with previous results. ILD is an important risk and requires careful recognition and intervention.
Clinical trial identification
NCT03384940.
Editorial acknowledgement
Legal entity responsible for the study
Daiichi Sankyo Co., Ltd.
Funding
Daiichi Sankyo Co., Ltd.
Disclosure
T. Yoshino: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Eli Lilly Japan K.K.; Bayer Yakuhin, Ltd.; Merck Biopharma Co., Ltd.; Takeda Pharmaceutical Company Limited; Research grant/Funding (institution): MSD K.K.; Ono Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; Sumitomo Dainippon Pharma Co., Ltd; Parexel International Inc.; Sanofi K.K.; Amgen K.K. S. Siena: Advisory/Consultancy, Travel/Accommodation/Expenses, Licensing/Royalties: Amgen; Advisory/Consultancy: Roche/Genetech; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Bristol-Myers Squibb; Clovis Oncology; Daiichi Sankyo; Incyte; Merck; Novartis; Seattle Genetics; CheckmAb; Research grant/Funding (institution): MSD Oncology; Travel/Accommodation/Expenses: Roche; Shareholder/Stockholder/Stock options: Guardant Health; Shareholder/Stockholder/Stock options: Myriad Genetics. M. Di Bartolomeo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Eli Lilly SpA; Honoraria (self), Speaker Bureau/Expert testimony: MSD; Honoraria (self): Merck Serono; Honoraria (self): Servier; Travel/Accommodation/Expenses: Roche. K. Raghav: Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: AstraZeneca. T. Masuishi: Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Merck Serono; Honoraria (self): Chugai Pharma; Honoraria (self): Yakult ; Honoraria (self): Takeda; Honoraria (self): Eli Lilly; Honoraria (self): Bayer Yakuhin; Honoraria (self): Sanofi; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Ono Pharmaceutical. F. Loupakis: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono. H. Kawakami: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Eli Lilly Japan; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self): Takeda; Honoraria (self), Advisory/Consultancy: MSD KK; Research grant/Funding (institution): Eisai. K. Yamaguchi: Honoraria (institution): Daiichi Sankyo; Honoraria (institution): Taiho Pharmaceutical; Honoraria (institution): Chugai Pharma; Honoraria (institution): Ono Pharmaceutical; Honoraria (institution): Eli Lilly; Honoraria (institution): Sanofi; Honoraria (institution): MSD; Honoraria (institution): Sumitomo Dainippon Pharma; Honoraria (institution): Gilead Sciences; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Eisai; Honoraria (institution): Yakult; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Japan; Speaker Bureau/Expert testimony: Takeda. T. Nishina: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Merck Serono; Honoraria (self): Takeda; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Nihonkayaku; Research grant/Funding (institution): Sumitomo Dainippon Pharma; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Ono Pharmaceutical. M. Fakih: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Advisory/Consultancy: Array BioPharma; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: Guardant360; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca. E. Elez: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: F. Hoffman-La Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Servier; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Array Biopharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Honoraria (institution): MSD; AbbVie; GSK; AstraZeneca; Novartis; Boehringer Ingelheim. F. Ciardiello: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Pierre; Research grant/Funding (institution): Ipsen. K. Saxena; E. Yamamoto; K. Kobayashi; E. Bako; Y. Okuda: Full/Part-time employment, employee: Daiichi Sankyo. A. Grothey: Honoraria (self): Elsevier; Aptitude Health; Imedex; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boston Biomedical; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Array BioPharma; Advisory/Consultancy: Guardant Health; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Eisai; Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.
Resources from the same session
80MO - Gut microbiome analysis for predicting neoadjuvant chemoradiotherapy response in locally advanced rectal cancer patients
Presenter: Yuxi Yi
Session: Mini oral session on Gastrointestinal tumours 2
Resources:
Abstract
Slides
Webcast
81MO - Clinical experience of a personalized and tumour-informed circulating tumour DNA assay for minimal residual disease detection in oligometastatic colorectal cancer patients
Presenter: Stacey Cohen
Session: Mini oral session on Gastrointestinal tumours 2
Resources:
Abstract
Slides
Webcast
82MO - Automatical risk stratifying for colorectal cancer by deep learning based pathological score
Presenter: Shenlun Chen
Session: Mini oral session on Gastrointestinal tumours 2
Resources:
Abstract
Slides
Webcast
83MO - AMG 510, a novel small molecule inhibitor of KRAS(G12C), for patients (pts) with advanced gastrointestinal (GI) cancers: Results from the CodeBreaK100 phase I trial
Presenter: Timothy Price
Session: Mini oral session on Gastrointestinal tumours 2
Resources:
Abstract
Slides
Webcast
85MO - Management of adverse events associated with encorafenib plus cetuximab in patients with BRAF V600E mutant metastatic colorectal cancer (BEACON CRC Study)
Presenter: Chang-Fang Chiu
Session: Mini oral session on Gastrointestinal tumours 2
Resources:
Abstract
Slides
Webcast
Invited Discussant abstracts 80MO, 81MO and 82MO
Presenter: Dawn Qing Qing Chong
Session: Mini oral session on Gastrointestinal tumours 2
Resources:
Slides
Webcast
Invited Discussant abstracts 83MO, 84MO and 85MO
Presenter: Julien Taieb
Session: Mini oral session on Gastrointestinal tumours 2
Resources:
Slides
Webcast
LIVE Q&A
Presenter: Julien Taieb
Session: Mini oral session on Gastrointestinal tumours 2
Resources:
Webcast
LIVE Q&A
Presenter: Julien Taieb
Session: Mini oral session on Gastrointestinal tumours 2
Resources:
Webcast