TY - JOUR
T1 - Targeting her2 with trastuzumab deruxtecan
T2 - A dose-expansion, phase i study in multiple advanced solid tumors
AU - Tsurutani, Junji
AU - Iwata, Hiroji
AU - Krop, Ian
AU - Jänne, Pasi A.
AU - Doi, Toshihiko
AU - Takahashi, Shunji
AU - Park, Haeseong
AU - Redfern, Charles
AU - Tamura, Kenji
AU - Wise-Draper, Trisha M.
AU - Saito, Kaku
AU - Sugihara, Masahiro
AU - Singh, Jasmeet
AU - Jikoh, Takahiro
AU - Gallant, Gilles
AU - Li, Bob T.
N1 - Funding Information:
This study was funded by Daiichi Sankyo Co., Ltd. B.T. Li is supported by the NIH/NCI Cancer Center Support Grant/Core Grant (P30 CA008748) at Memorial Sloan Kettering Cancer Center.
Funding Information:
Corp, LOXO Oncology, and Gatekeeper Pharmaceuticals. S. Taka-hashi reports receiving commercial research grants from Daiichi San-kyo, Sanofi, Lilly, Ono Pharmaceutical, Pfizer, Astellas Pharma, Eisai, Bayer, Taiho, MSD, Novartis, Chugai Pharma, AstraZeneca, and Bristol-Myers Squibb, and has received speakers bureau honoraria from Daiichi Sankyo, Sanofi, Ono Pharmaceutical, Nihonkayaku, Eisai, Bayer, Taiho Pharmaceutical, MSD, Novartis, Chugai Pharma, Astra-Zeneca, and Bristol-Myers Squibb. H. Park reports receiving a commercial research grant from Daiichi Sankyo. K. Saito is a manager at Daiichi Sankyo. M. Sugihara is a manager at Daiichi-Sankyo Co., Ltd. T. Jikoh is a global deputy team leader for DS-8201a for Daiichi Sankyo, Inc. G. Gallant is senior vice president, global head, oncology development, at Daiichi Sankyo. B.T. Li is a consultant/advisor at Biosceptre International, Guardant Health, Hengrui Therapeutics, Mersana, Thermo Fisher Scientific, and Roche/Genentech, reports receiving commercial research grants from AstraZeneca, BioMed Valley Discoveries, MORE Health, Daiichi Sankyo, GRAIL, Guardant Health, Hengrui Therapeutics, Illumina, Amgen, Lilly, and Roche/Genentech, and has ownership interest in institutional patents at Memorial Sloan Kettering Cancer Center (US62/685,05, US62/514,661). No potential conflicts of interest were disclosed by the other authors.
Funding Information:
J. Tsurutani reports receiving commercial research grants from Eisai, Kyowa Kirin, Daiichi Sankyo, Eli Lilly, Nihon Kayaku, Chugai, Pfizer, and MSD, has received speakers bureau honoraria from Eisai, Kyowa Kirin, Taiho, Chugai, Eli Lilly, Novartis, Daiichi Sankyo, and Nihon Kayaku, and has cosultant/advisory board relationships with Daiichi Sankyo, Eli Lilly, and Asahi Kasei. H. Iwata is a consultant at Chugai, Pfizer, Novartis, Daiichi Sankyo, AstraZeneca, Lilly, Kyowa Hakko Kirin, AbbVie, and Odonate, and has received speakers bureau honoraria from Chugai/Roche, Daiichi Sankyo, AstraZeneca, Lilly, Pfizer, Novartis, Taiho, and Eisai. I. Krop is a consultant at Daiichi Sankyo, AstraZeneca, Genentech Roche, Context Therapeutics, Mac-rogenics, Bristol-Myers Squibb, Seattle Genetics, and Taiho Oncology, has received speaking fees from Celltrion, and has received other remuneration from Merck and Novartis. P.A. Janne is a consultant at AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Pfizer, ACEA Biosciences, Eli Lilly, Araxes Biosciences, SFJ Pharmaceuticals, Dai-ichi Sankyo, Novartis, Sanofi Oncology, and Takeda Oncology, is an SAB member at Biocartis, Ignyta, LOXO Oncology, Voronoi, and Mirati Therapeutics, reports receiving commercial research grants from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, PUMA, Eli Lilly, Revolution Medicines, Takeda Oncology, and Astellas Pharmaceuticals, and has ownership interest (including patents) in Lab
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/5
Y1 - 2020/5
N2 - HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting. Two drug-related TEAEs were associated with fatal outcomes. The confirmed objective response rate (ORR) was 28.3% (17/60). Median progression-free survival (PFS) was 7.2 [95% confidence interval (CI), 4.8–11.1] months. In HER2-mutant non–small cell lung cancer (NSCLC), ORR was 72.7% (8/11), and median PFS was 11.3 (95% CI, 8.1–14.3) months. Confirmed responses were observed in six tumor types, including HER2-expressing NSCLC, colorectal cancer, salivary gland cancer, biliary tract cancer, endometrial cancer, and HER2-mutant NSCLC and breast cancer. Results suggest T-DXd holds promise for HER2-expressing/mutant solid tumors. SIGnIfICAnCE: T-DXd demonstrated promising activity in a heterogeneous patient population with heavily pretreated HER2-expressing or HER2-mutant solid tumors, especially HER2-mutant NSCLC. The safety profile was generally acceptable. Interstitial lung disease can be severe and requires prompt monitoring and intervention. Further research of T-DXd is warranted to address these unmet medical needs.
AB - HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting. Two drug-related TEAEs were associated with fatal outcomes. The confirmed objective response rate (ORR) was 28.3% (17/60). Median progression-free survival (PFS) was 7.2 [95% confidence interval (CI), 4.8–11.1] months. In HER2-mutant non–small cell lung cancer (NSCLC), ORR was 72.7% (8/11), and median PFS was 11.3 (95% CI, 8.1–14.3) months. Confirmed responses were observed in six tumor types, including HER2-expressing NSCLC, colorectal cancer, salivary gland cancer, biliary tract cancer, endometrial cancer, and HER2-mutant NSCLC and breast cancer. Results suggest T-DXd holds promise for HER2-expressing/mutant solid tumors. SIGnIfICAnCE: T-DXd demonstrated promising activity in a heterogeneous patient population with heavily pretreated HER2-expressing or HER2-mutant solid tumors, especially HER2-mutant NSCLC. The safety profile was generally acceptable. Interstitial lung disease can be severe and requires prompt monitoring and intervention. Further research of T-DXd is warranted to address these unmet medical needs.
UR - http://www.scopus.com/inward/record.url?scp=85084961404&partnerID=8YFLogxK
U2 - 10.1158/2159-8290.CD-19-1014
DO - 10.1158/2159-8290.CD-19-1014
M3 - Article
C2 - 32213540
AN - SCOPUS:85084961404
VL - 10
SP - 688
EP - 701
JO - Cancer Discovery
JF - Cancer Discovery
SN - 2159-8274
IS - 5
ER -