AstraZeneca and Daiichi Sankyo announce that Phase II trial DESTINY-Gastric01 reached the primary end point in patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer.
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.
The trial met its primary endpoint of an improvement in ORR, as assessed by an independent review committee, in patients treated with Enhertu compared to investigator’s choice of chemotherapy (irinotecan or paclitaxel monotherapy). Enhertu also showed a statistically significant and clinically meaningful improvement in OS, a key secondary endpoint.
José Baselga, Executive Vice President, Oncology R&D, said: “Gastric cancer is usually diagnosed in the advanced stage and patients face markedly high mortality rates, making the need for new therapies especially urgent. Given the previous results seen in our HER2-positive development programme and now in HER2-positive metastatic gastric cancer, we believe this antibody drug conjugate has the potential to redefine the treatment of patients with HER2-expressing cancers.”
Gilles Gallant, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo, said: “We are excited to report positive top-line results from this trial. Our development plan remains on track in gastric cancer, including an initial regulatory application in Japan where gastric cancer is highly prevalent, and where SAKIGAKE designation has been granted for this indication. We are strongly committed to bringing this therapy as rapidly as possible to patients in need.”
The overall safety and tolerability profile of Enhertu in DESTINY-Gastric01 was consistent with that seen in the published Phase I trial in which the most common adverse events (≥30 percent, any grade) were haematologic and gastrointestinal including neutrophil count decrease, anaemia, nausea and decreased appetite. There were cases of treatment-related interstitial lung disease (ILD) and pneumonitis, the majority of which were Grade 1 and 2 with two Grade 3 and one Grade 4. No ILD-related deaths (Grade 5) occurred in gastric patients in the Phase I trial or in the DESTINY-Gastric01 trial.
These results confirm activity seen in the non-randomised Phase I trial of Enhertu in patients with HER2-positive advanced gastric cancer published in The Lancet Oncology.1 Data from DESTINY-Gastric01 will be presented at a forthcoming medical meeting.
In addition to the planned discussion with the Japan Ministry of Health, Labour and Welfare (MHLW), both companies plan to discuss the data with other health authorities. Enhertu recently received Accelerated Approval in the US for HER2-positive unresectable or metastatic breast cancer following two or more prior anti-HER2 based treatment regimens and additional global regulatory submissions in HER2-positive metastatic breast cancer are underway.
Enhertu is being jointly developed and commercialised worldwide with AstraZeneca except in Japan where Daiichi Sankyo maintains exclusive rights.