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.

Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced the approval of ENHERTU® (trastuzumab deruxtecan), a HER2 directed antibody drug conjugate (ADC), in Japan for the treatment of patients with HER2 positive unresectable advanced or recurrent gastric cancer that has progressed after chemotherapy.

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.

AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s Enhertu (trastuzumab deruxtecan) has been granted Breakthrough Therapy Designation (BTD) in the US 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.

...For Part 1, 2, 3a, pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local tissue testing results 3....

...- 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....

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

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

...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....

...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. ...

...Disease Characteristics: a/Locally advanced, unresectable, or metastatic disease based on most recent imagingb/For Part 1, 2, 3a, pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local tissue testing resultsc/For Part 3b, pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-low (IHC 2+/ISH-negative or IHC 1+) based on local tissue testing results3. ...

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.

In this multicenter retrospective study, we collected clinical data of HER2 positive AGC patients received T-DXd...In all patients, response rate (RR) was 42%, disease control rate was 78%, median progression free survival (PFS) was 4 months (95% CI: 2.6-6.5) and median overall survival (OS) was 6.1 months (95%CI:3.7-9.4)….

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.

DG-01 primary cohort enrolled pts who progressed on ≥2 prior lines with centrally confirmed HER2+ AGC....This exploratory analysis suggests that treatment with T-DXd results in better outcomes than chemotherapy regardless of prior ICI.

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.

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

...In an exploratory analysis, both patient subgroups showed a response to T-DXd; ORRs were 48.8% and 56.8%, respectively...clinically meaningful efficacy of T-DXd was demonstrated in HER2+ AGC.

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.

OS was significantly prolonged with T-DXd (median OS, 12.5 vs 8.4 months; HR, 0.59 [95% CI, 0.39-0.88]; P =.0097;...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.

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.

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

...enrolls subjects (sbj) with HER2+ breast cancer (BC) post T-DM1, HER2+ gastric cancer (GC) post trastuzumab, HER2 low BC (IHC 1+ or 2+, ISH-), and other HER2-expressing solid tumors (IHC ≥1+)….Overall, RECIST-confirmed overall response rate (ORR) in the evaluable sbj was 81/160 (50.6%) with the highest ORR in HER2+ BC (64.2%)....DS-8201a shows antitumor activity in multiple tumor types with high ORR and durable responses in heavily pretreated sbj.

This is a case of a 65-year-old man with human epidermal growth factor-2 (HER2)-positive AGC….In August 2020, following the approval of T-DXd for HER2-positive AGC, he received T-DXd therapy. After 5 cycles of T-DXd, contrast-enhanced computed tomography and magnetic resonance imaging demonstrated significant tumor shrinkage and improvement of symptoms.