Phase II registrational trial of Enhertu to treat HER2-positive unresectable or metastatic gastric or gastroesophageal junction cancer . AstraZeneca + Daiichi Sankyo

High-level results from the positive registrational Phase II trial DESTINY-Gastric01 showed AstraZeneca’s and Daiichi Sankyo Company, Limited '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.” 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 . Data from DESTINY-Gastric01 will be presented at a forthcoming medical meeting. DESTINY-Gastric01 trial : DESTINY-Gastric01 is a registrational Phase II, open-label, multi-centre trial assessing the safety and efficacy of Enhertu in 189 patients from Japan and South Korea with HER2-expressing advanced gastric cancer or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have progressed on two or more prior treatment regimens including fluoropyrimidine (5-FU) and platinum chemotherapy and trastuzumab. Patients were randomised 2:1 to receive Enhertu or investigator’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with Enhertu 6.4mg/kg once every three weeks or chemotherapy given on the same schedule. The primary endpoint of the trial is ORR. Secondary endpoints include OS, progression-free survival, duration of response, disease control rate and time to treatment failure as well as pharmacokinetic and safety endpoints. See- Shitara K et al. Lancet Oncol. 2019; S1470-2045 (19):30088-9.