Daiichi Sankyo and AstraZeneca’s ENHERTU® (trastuzumab deruxtecan) has been approved in the European Union (EU) as a monotherapy for the treatment of adult patients with advanced HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen....The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use in November 2022 and is based on results from the DESTINY-Gastric02 and DESTINY-Gastric01 phase 2 trials.

Enhertu, a new breast and stomach cancer treatment, has won domestic approval...The domestic approval of Enhertu aims to treat non-abstractable or metastatic HER2-positive breast cancer patients with two or more administrations of HER2-based treatments, and locally progressive or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma patients with two or more administrations of treatments, including anti-HER2 treatment.

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of...adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

For HER2-positive patients with gastric or GEJ AC who have progressed after first-line therapy, trastuzumab deruxtecan is recommended.

AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s Enhertu (trastuzumab deruxtecan) has received acceptance for its supplemental Biologics License Application (sBLA) and has also been granted Priority Review in the US for the treatment of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

...Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca’s ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been granted Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of patients with HER2 positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have received two or more prior regimens including trastuzumab.

...Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)`Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)`Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)`Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)`Best Overall Response By The Investigator's Assessment (Unconfirmed) in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer`Objective Response Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer`Disease Control Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer...

...Key Inclusion Criteria:- Men or women ≥18 years old (Please follow local regulatory requirements if the legal age of consent for study participation is >18 years old.)- Has pathologically documented gastric or GEJ cancer that is: - Unresectable or metastatic - Centrally confirmed HER2-positive disease (immunohistochemistry [IHC]3+, IHC2+/in-situ hybridization [ISH]+) as determined according to American Society of Clinical Oncology – College of American Pathologists (ASCO-CAP) guidelines based on a new tissue sample obtained after progression on or after a trastuzumabcontaining regimen. ...

...- Histological or cytological confirmed diagnosis of advanced HER2 positive gastric cancer or GEJ...

...- Has pathologically documented HER2-positive gastric or GEJ cancer that is unresectable or metastatic, and that progressed during or after treatment regimen containing trastuzumab...

...HER2-positive other solid tumors included participants with salivary/submandibular/parotid gland (8 participants), breast with HER2-mutation (2 participants), endometrial (2 participants), esophageal (2 participants), Paget's disease (2 participants), cholangiocarcinoma (1 participant), extraskeletal myxoide chondrosarcoma (1 participant), gallbladder (1 participant), pancreatic (1 participant), small intestine (1 participant), uterine cervix (1 participant) and HER2-low gastric/GEJ (1 participant who received 5.4 mg/kg) cancer....

...- Locally or centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH) as classified by ASCO-CAP on a tumor biopsy obtained after progression on or after a first-line trastuzumab or approved trastuzumab biosimilar-containing regimen....

This primary analysis of T-DXd in Chinese pts with HER2-positive advanced GC/GEJA demonstrated clinically meaningful and durable objective responses, with a manageable safety profile, and is consistent with results from DG01.

Median OS was significantly longer among patients treated with T-DXd (11.6 months, 95%CI: 9.0-20.5) compared to the Ram+Pac group (6.2 months, 95%CI: 4.5 – 10.0) (HR: 0.39, 95%CI: 0.26 –0.59, p<0.0001)….Compared to propensity score-matched patients with metastatic, trastuzumab-pretreated HER2+ gastric or GEJ adenocarcinomas who received Ram+Pac in the real-world as a second -line therapy, overall survival was better for patients who received T-DXd.

In the efficacy population, the ORR and DCR were 76.3% and 94.7%, respectively. The overall median PFS was 9.1 months (95% confidence interval [CI] 6.3-11.9 months)...This real-world study validated the combination regimen's high efficacy and good tolerance in patients with HER2-positive gastric/GEJ cancer.

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been recommended for approval in the European Union (EU) as monotherapy for the treatment of adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen...The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the DESTINY-Gastric02 and the DESTINY-Gastric01 Phase II trials.

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

With additional follow-up after the primary analysis, T-DXd continued to demonstrate OS benefit and clinically relevant improvement in ORR compared with standard chemotherapy, and a manageable safety profile, in HER2–positive advanced GC or GEJ adenocarcinoma.

Preliminary confirmed and confirmed + unconfirmed ORR at the RP2D for T-DXd + Cap were 3/7 and 5/7, respectively; 3/3 pts at the starting dose of T-DXd + Cap had confirmed ORR...Preliminary ORR with the T-DXd + Cap RP2D (n = 7) showed efficacy with this combination in heavily pretreated, trastuzumab- and fluoropyrimidine-refractory, HER2+ GC/GEJA.

OS was improved with T-DXd vs PC (median OS, 12.5 vs 8.9 mo; hazard ratio [HR], 0.60 [95% CI, 0.42-0.86]); 12-month OS, 52.2% vs 29.7%. ORR was 51.3% (61/119; 11 CR; 50 PR) with T-DXd vs 14.3% (8/56; all PR) with PC (P< 0.0001); confirmed ORR, 42.0% (50/119; 10 CR; 40 PR) vs 12.5% (7/56; all PR) (P= 0.0001); DCR, 85.7% vs 62.5% (P= 0.0005); confirmed median DOR, 12.5 vs 3.9 mo; median PFS, 5.6 vs 3.5 mo (HR, 0.47 [95% CI, 0.31-0.71]; P= 0.0003)....T-DXd continued to demonstrate OS benefit and clinically relevant improvement in ORR compared with standard chemotherapy, and a manageable safety profile, in HER2–positive advanced GC or GEJ adenocarcinoma.

T-DXd demonstrated clinical efficacy and a manageable safety profile in 2L treatment of Western patients with HER2+ unresectable/metastatic gastric/GEJ cancer.

OS was improved with T-DXd vs PC (median OS, 12.5 vs 8.9 mo; hazard ratio [HR], 0.60 [95% CI, 0.42-0.86]); 12-month OS, 52.2% vs 29.7%. ORR was 51.3% (61/119; 11 CR; 50 PR) with T-DXd vs 14.3% (8/56; all PR) with PC (P< 0.0001); confirmed ORR, 42.0% (50/119; 10 CR; 40 PR) vs 12.5% (7/56; all PR) (P = 0.0001); DCR, 86.6% vs 62.5% (P = 0.0003); confirmed median DOR, 12.5 vs 3.9 mo; median PFS, 5.6 vs 3.5 mo (HR, 0.47 [95% CI, 0.31-0.71]; P = 0.0003)....With additional follow-up after the primary analysis, T-DXd continued to demonstrate OS benefit and clinically relevant improvement in ORR compared with standard chemotherapy, and a manageable safety profile, in HER2-positive advanced GC or GEJ adenocarcinoma.

Patients with centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma that had progressed while they were receiving at least two previous therapies, including trastuzumab, were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan...An objective response was reported in 51% of the patients in the trastuzumab deruxtecan group, as compared with 14% of those in the physician’s choice group (P<0.001). Overall survival was longer with trastuzumab deruxtecan than with chemotherapy (median, 12.5 vs. 8.4 months; hazard ratio for death, 0.59; 95% confidence interval, 0.39 to 0.88; P=0.01...Therapy with trastuzumab deruxtecan led to significant improvements in response and overall survival, as compared with standard therapies, among patients with HER2-positive gastric cancer.

In a randomized phase II trial of HER2-positive gastric and gastroesophageal junction cancers, the agent significantly extended overall survival and progression-free survival compared with standard chemotherapy.

T-DXd demonstrated statistically significant and clinically meaningful improvements in ORR and OS compared with standard chemotherapy (paclitaxel or irinotecan) in patients with HER2+ advanced gastric or GEJ adenocarcinoma.

High-level results from the positive registrational Phase II trial DESTINY-Gastric01 showed AstraZeneca’s and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s Enhertu (trastuzumab deruxtecan), achieved a statistically significant and clinically meaningful improvement in objective response rate (ORR) and overall survival (OS) in patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer that had progressed following two or more treatment regimens including trastuzumab and chemotherapy.

Trastuzumab deruxtecan had a manageable safety profile and showed preliminary activity in heavily pretreated patients with HER2-positive gastric or gastro-oesophageal junction cancer.