AstraZeneca and Daiichi Sankyo on Wednesday presented detailed results from a pivotal Phase II study showing that monotherapy with trastuzumab deruxtecan, also known as DS-8201, led to an objective response rate of 60.9% in patients with HER2-positive metastatic breast cancer who received two or more prior HER2-targeted regimens. Data on the experimental antibody drug conjugate (ADC) were announced at the San Antonio Breast Cancer Symposium (SABCS) and simultaneously published in the NEJM.
In May, the companies reported that the DESTINY-Breast01 trial met its primary endpoint, with the FDA recently granting a priority review to a filing for trastuzumab deruxtecan. The therapy is also under review by Japanese regulators.
The companies noted that in the study, patients had undergone a median of six prior lines of therapy for metastatic disease, including with Roche's ADC Kadcyla (trastuzumab emtansine). José Baselga, executive vice president of oncology R&D at AstraZeneca, said the observed clinical benefit was "totally unprecedented," adding that "clinically meaningful and durable responses seen among these patients illustrate the potential of trastuzumab deruxtecan to establish a new standard of care."
Results from the latest analysis involving 184 evaluable patients also showed a disease control rate of 97.3% with a median duration of response of 14.8 months and median progression-free survival of 16.4 months. AstraZeneca noted that the median overall survival (OS) has not yet been reached, but the OS rate is estimated to be 86% at one year. Complete and partial responses occurred at rates of 6% and 54.9%, respectively, with the companies adding that efficacy findings were consistent across subgroups of patients.
Meanwhile, the safety and tolerability profile of trastuzumab deruxtecan in the trial was also consistent with that observed in early-stage testing. However, the study authors noted that in addition to nausea and myelosuppression, "interstitial lung disease (ILD) was observed in a subgroup of patients and requires attention to pulmonary symptoms and careful monitoring." Overall, 13.6% of patients had confirmed ILD related to treatment. The companies said the events were primarily Grades 1 or 2 in severity, with one Grade 3 event, but there were four ILD-related deaths in the study.
In March, AstraZeneca agreed to pay Daiichi Sankyo $1.35 billion upfront as part of a deal potentially worth up to $6.9 billion to jointly develop and commercialise trastuzumab deruxtecan. Further trials will assess the therapy in earlier lines of treatment in breast cancer, in addition to lung and gastric cancer. "If this benefit is observed in this line of therapy, I think that this drug can be incredibly beneficial in patients with earlier disease," Baselga remarked.
For further analysis, read ViewPoints: AstraZeneca's big bet on Daiichi Sankyo comes home.
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