1422MO - Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-low, advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Results of the exploratory cohorts in the phase II, multicenter, open-label DESTINY-Gastric01 study

Background

T-DXd is an antibody-drug conjugate consisting of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a membrane-permeable topoisomerase I inhibitor payload. T-DXd is approved for the treatment of HER2-positive metastatic breast cancer in the US and Japan. T-DXd increased confirmed ORR (42.9% vs 12.5%) and OS (median, 12.5 vs 8.4 mo; HR, 0.59; P = .0097) vs chemotherapy in patients (pts) with HER2+ (IHC 3+; IHC 2+/ISH +) metastatic gastric or GEJ cancer in the primary cohort in the DESTINY-Gastric01 open-label, multicenter, phase II trial (NCT03329690). We present results from the HER2-low exploratory cohorts.

Methods

Pts with centrally confirmed HER2-low (IHC 2+/ISH− [cohort 1] or IHC 1+ [cohort 2] on archival tissue) that progressed on ≥ 2 prior lines of therapy were enrolled in Japan and Korea. Pts were excluded if they had prior HER2 therapy. The primary endpoint was ORR by independent central review.

Results

20 (cohort 1) and 24 (cohort 2) pts were treated with T-DXd 6.4 mg/kg q3w. Most were from Japan (cohort 1, 80.0%; cohort 2, 79.2%) and had received a median of 2 prior lines of therapy. At data cutoff (8 Nov 2019), no pts in cohort 1 and 2 in cohort 2 (8.3%) remained on treatment (median duration, 4.2 and 2.8 mo). In cohort 1, confirmed ORR was 26.3% (5/19, all PR); 12 pts had stable disease (DCR, 89.5%). Median PFS was 4.4 mo (95% CI, 2.7-7.1 mo); median OS was 7.8 mo (95% CI, 4.7 mo-NE), with a 12-mo OS rate of 40.0%. Confirmed ORR in cohort 2 was 9.5% (2/21, all PR); confirmed DCR was 71.4%. Median PFS and OS were 2.8 mo (95% CI, 1.5-4.3 mo) and 8.5 mo (95% CI, 4.3-10.9 mo), with a 12-mo OS rate of 25.7%. Grade ≥ 3 adverse events occurred in 70.0% and 79.2% of pts in cohorts 1 and 2. Decreased appetite (65.0%; 75.0%), nausea (55.0%; 79.2%), and neutrophil count decreased (45.0%; 50.0%) were most common. One pt in each cohort (grade 1 = 1; grade 2 = 1) had T-DXd–related interstitial lung disease.

Conclusions

T-DXd showed preliminary evidence of clinical activity in pts with previously treated, HER2-low gastric or GEJ cancer. The safety profile was similar to that in the HER2+ primary cohort.

Clinical trial identification

NCT03329690.

Editorial acknowledgement

Medical editorial assistance provided by John Togneri, PhD (Articulate Science LLC).

Legal entity responsible for the study

Daiichi Sankyo Co., Ltd.

Funding

Daiichi Sankyo Co., Ltd.

Disclosure

K. Yamaguchi: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Cancer Institute Hospital of Japanese Foundation for Cancer Research; Honoraria (institution), Speaker Bureau/Expert testimony: Daiichi Sankyo ; Honoraria (institution), Speaker Bureau/Expert testimony: Taiho Pharmaceutical; Honoraria (institution), Speaker Bureau/Expert testimony: Chugai Pharm; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Japan; Honoraria (institution), Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Takeda; Honoraria (institution), Speaker Bureau/Expert testimony: Lilly; Honoraria (institution), Speaker Bureau/Expert testimony: Sanofi; Honoraria (institution): MSD oncology; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Gilead Sciences; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Eisai; Honoraria (institution): Yakult Honsha. Y-J. Bang: Advisory/Consultancy: Samyung; Advisory/Consultancy, Research grant/Funding (institution): BeiGene; Advisory/Consultancy, Research grant/Funding (institution): Green Cross; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca/MedImmune; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Hanmi; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Genexine; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Five Prime Therapeutics; Research grant/Funding (institution): Chong Kun Dang Pharmaceutical; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Curis. S. Iwasa: Research grant/Funding (institution): Daiichi Sankyo . N. Sugimoto: Research grant/Funding (institution): Daiichi Sankyo ; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Solasia; Research grant/Funding (institution): ONO; Research grant/Funding (self): Lilly; Research grant/Funding (self): Taiho. M-H. Ryu: Honoraria (self), Advisory/Consultancy: ONO; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Lilly ; Honoraria (self), Advisory/Consultancy: Taiho; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Daehwa Pharmaceutical . D. Sakai: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai Pharma; Research grant/Funding (institution): Yakult Honsha; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Lilly Japan. H.C. Chung: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck-Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy: Celltrion; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Quintiles; Advisory/Consultancy, Research grant/Funding (institution): BMS/Ono; Advisory/Consultancy, Research grant/Funding (institution): Beigene; Advisory/Consultancy: Gloria; Advisory/Consultancy: AMGEN; Research grant/Funding (institution): GSK. H. Kawakami: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Bristol and 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; Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy: MSD KK. J. Lee: Advisory/Consultancy: Oncologie; Advisory/Consultancy: Seattle Genetics; Research grant/Funding (self): Astra Zeneca; Research grant/Funding (self): Merck Sharp and Dohme; Research grant/Funding (self): Eli Lilly and Company. K. Saito, T. Kamio, M. Sugihara: Full/Part-time employment: Daiichi Sankyo. Y. Kawaguchi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo . A. Kojima: Shareholder/Stockholder/Stock options, Full/Part-time employment: Daiichi Sankyo . K. Shitara: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Abbvie; Honoraria (self): Yakult; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutica; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharm; Research grant/Funding (institution): Medi Science; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dainippon Sumitomo Pharma. All other authors have declared no conflicts of interest.