AstraZeneca, Daiichi Sankyo’s Enhertu receives priority review status in US treat HER2-positive metastatic gastric cancer
AstraZeneca and 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.
Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality with a five-year survival rate of 5% for metastatic disease; there were approximately one million new cases reported in 2018 and 783,000 deaths. In the US, it is estimated that 27,600 new cases of gastric cancer will be diagnosed in 2020 and more than 11,000 people will die from the disease. For patients with metastatic gastric cancer who progress on initial treatment with an anti-HER2 medicine, there are no other approved HER2-directed medicines.
José Baselga, executive vice president, Oncology R&D said, “Once patients with HER2-positive metastatic gastric cancer progress following initial treatment with an anti-HER2 regimen, there are no approved HER2-directed medicines. The prognosis for these patients is poor, as available treatment options offer only limited clinical benefit. This milestone brings us one step closer to delivering a potentially practice-changing medicine to patients with gastric cancer in the US.”
Antoine Yver, executive vice president and global head, Oncology Research and Development, Daiichi Sankyo said, “The results of the DESTINY-Gastric01 trial are unprecedented as they represent the first time a HER2-directed medicine has demonstrated an improvement in survival following chemotherapy and HER2 treatment in the metastatic setting. Building on the recent Breakthrough Therapy Designation, the filing of the application and Priority Review by the US FDA for this potential new indication for Enhertu reflects the importance of the data and the significant unmet need for patients with previously treated HER2-positive metastatic gastric cancer.”
The sBLA was based on results from the DESTINY-Gastric01 randomised phase II trial, which demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR), the primary endpoint, and overall survival (OS), a key secondary endpoint, for patients treated with Enhertu versus chemotherapy (paclitaxel or irinotecan monotherapy).
The safety and tolerability profiles of Enhertu in DESTINY-Gastric01 were consistent with that observed in the gastric cancer cohort of the phase I trial and previously reported Enhertu trials in other tumours. The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count, anaemia, decreased white blood cell count and decreased appetite. There were 12 (9.6%) cases of confirmed treatment-related interstitial lung disease (ILD) or pneumonitis in 125 patients treated with Enhertu as determined by an independent review committee. The majority of cases were Grade 1 or 2 with two Grade 3, one Grade 4 and no Grade 5 (ILD-related deaths).
Approximately one in five gastric cancers are HER2 positive. HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers. Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease, the survival rate remains modest. Recommended 1st-line treatment for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy. For metastatic gastric cancer that progresses on 1st-line treatment, there are no other approved HER2-targeted medicines.
DESTINY-Gastric01 is a phase II, open-label, multi-centre, randomised controlled trial testing the safety and efficacy of Enhertu versus investigator’s choice of chemotherapy in a primary cohort of 188 patients from Japan and South Korea with HER2-positive (defined as IHC3+ or IHC2+/ISH+), advanced gastric or GEJ adenocarcinoma who have progressed on two or more prior treatment regimens including fluoropyrimidine 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.
Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the US) is a HER2-directed antibody drug conjugate (ADC) and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (‘payload’) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.
Source:http://www.pharmabiz.com/NewsDetails.aspx?aid=133113&sid=2
Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality with a five-year survival rate of 5% for metastatic disease; there were approximately one million new cases reported in 2018 and 783,000 deaths. In the US, it is estimated that 27,600 new cases of gastric cancer will be diagnosed in 2020 and more than 11,000 people will die from the disease. For patients with metastatic gastric cancer who progress on initial treatment with an anti-HER2 medicine, there are no other approved HER2-directed medicines.
José Baselga, executive vice president, Oncology R&D said, “Once patients with HER2-positive metastatic gastric cancer progress following initial treatment with an anti-HER2 regimen, there are no approved HER2-directed medicines. The prognosis for these patients is poor, as available treatment options offer only limited clinical benefit. This milestone brings us one step closer to delivering a potentially practice-changing medicine to patients with gastric cancer in the US.”
Antoine Yver, executive vice president and global head, Oncology Research and Development, Daiichi Sankyo said, “The results of the DESTINY-Gastric01 trial are unprecedented as they represent the first time a HER2-directed medicine has demonstrated an improvement in survival following chemotherapy and HER2 treatment in the metastatic setting. Building on the recent Breakthrough Therapy Designation, the filing of the application and Priority Review by the US FDA for this potential new indication for Enhertu reflects the importance of the data and the significant unmet need for patients with previously treated HER2-positive metastatic gastric cancer.”
The sBLA was based on results from the DESTINY-Gastric01 randomised phase II trial, which demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR), the primary endpoint, and overall survival (OS), a key secondary endpoint, for patients treated with Enhertu versus chemotherapy (paclitaxel or irinotecan monotherapy).
The safety and tolerability profiles of Enhertu in DESTINY-Gastric01 were consistent with that observed in the gastric cancer cohort of the phase I trial and previously reported Enhertu trials in other tumours. The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count, anaemia, decreased white blood cell count and decreased appetite. There were 12 (9.6%) cases of confirmed treatment-related interstitial lung disease (ILD) or pneumonitis in 125 patients treated with Enhertu as determined by an independent review committee. The majority of cases were Grade 1 or 2 with two Grade 3, one Grade 4 and no Grade 5 (ILD-related deaths).
Approximately one in five gastric cancers are HER2 positive. HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers. Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease, the survival rate remains modest. Recommended 1st-line treatment for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy. For metastatic gastric cancer that progresses on 1st-line treatment, there are no other approved HER2-targeted medicines.
DESTINY-Gastric01 is a phase II, open-label, multi-centre, randomised controlled trial testing the safety and efficacy of Enhertu versus investigator’s choice of chemotherapy in a primary cohort of 188 patients from Japan and South Korea with HER2-positive (defined as IHC3+ or IHC2+/ISH+), advanced gastric or GEJ adenocarcinoma who have progressed on two or more prior treatment regimens including fluoropyrimidine 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.
Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the US) is a HER2-directed antibody drug conjugate (ADC) and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (‘payload’) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.
Source:http://www.pharmabiz.com/NewsDetails.aspx?aid=133113&sid=2
Comments
Post a Comment