FDA News

FDA grants priority review to antibody-drug conjugate for HER2-positive metastatic breast cancer

José Baselga, MD, PhD
José Baselga

The FDA granted priority review to [fam-] trastuzumab deruxtecan for the treatment of patients with HER2-positive metastatic breast cancer, according to a press release from the agent’s manufacturer.

[Fam-] trastuzumab deruxtecan (DS-8201; Daiichi Sankyo, AstraZeneca) — an antibody-drug conjugate consisting of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker — is designed to deliver chemotherapy inside cancer cells to reduce systemic exposure to chemotherapy.

“We are pleased that the FDA has accepted the application and granted priority review, as we believe [fam-] trastuzumab deruxtecan has the potential to redefine the treatment of patients with HER2-positive metastatic breast cancer,” Antoine Yver, MD, MSc, executive vice president and global head of oncology research and development at Daiichi Sankyo, said in the press release. “Following the recent regulatory submission in Japan, we look forward to working closely with regulatory authorities to bring [fam-] trastuzumab deruxtecan to patients in the U.S. and Japan as soon as possible.”

The FDA based its decision, in part, on data from the pivotal phase 2, open-label, global, multicenter, two-part DESTINY-Breast01 trial, which will be presented at San Antonio Breast Cancer Symposium in December. The trial included 253 patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with ado-trastuzumab emtansine (Kadcyla, Genentech). Objective response rate served as the study’s primary endpoint, with duration of response, disease control rate, clinical benefit rate, PFS and OS as secondary endpoints.

The FDA also considered phase 1 trial dose-expansion data published in The Lancet Oncology, which showed an ORR of 59.5% (95% CI, 49.7-68.7) and a disease control rate of 93.7% (95% CI, 87.4-97.4) with [fam-] trastuzumab deruxtecan among 111 evaluable patients with HER2-positive metastatic breast cancer.

Both trials showed similar safety and tolerability profiles. The most common adverse events included nausea, decreased appetite, vomiting, alopecia, fatigue, anemia, diarrhea and constipation. Drug-related interstitial lung disease and pneumonitis, including grade 5 events, also have occurred.

“[Fam-] trastuzumab deruxtecan has the potential to transform the treatment landscape for patients with HER2-positive metastatic breast cancer who have limited treatment options,” José Baselga, MD, PhD, executive vice president of research and development oncology at AstraZeneca, said in the release. “The priority review draws on the strength and consistency of results seen in phase 1 and phase 2 trials and is an important step on the journey to deliver this potential new medicine to patients.”

José Baselga, MD, PhD
José Baselga

The FDA granted priority review to [fam-] trastuzumab deruxtecan for the treatment of patients with HER2-positive metastatic breast cancer, according to a press release from the agent’s manufacturer.

[Fam-] trastuzumab deruxtecan (DS-8201; Daiichi Sankyo, AstraZeneca) — an antibody-drug conjugate consisting of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker — is designed to deliver chemotherapy inside cancer cells to reduce systemic exposure to chemotherapy.

“We are pleased that the FDA has accepted the application and granted priority review, as we believe [fam-] trastuzumab deruxtecan has the potential to redefine the treatment of patients with HER2-positive metastatic breast cancer,” Antoine Yver, MD, MSc, executive vice president and global head of oncology research and development at Daiichi Sankyo, said in the press release. “Following the recent regulatory submission in Japan, we look forward to working closely with regulatory authorities to bring [fam-] trastuzumab deruxtecan to patients in the U.S. and Japan as soon as possible.”

The FDA based its decision, in part, on data from the pivotal phase 2, open-label, global, multicenter, two-part DESTINY-Breast01 trial, which will be presented at San Antonio Breast Cancer Symposium in December. The trial included 253 patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with ado-trastuzumab emtansine (Kadcyla, Genentech). Objective response rate served as the study’s primary endpoint, with duration of response, disease control rate, clinical benefit rate, PFS and OS as secondary endpoints.

The FDA also considered phase 1 trial dose-expansion data published in The Lancet Oncology, which showed an ORR of 59.5% (95% CI, 49.7-68.7) and a disease control rate of 93.7% (95% CI, 87.4-97.4) with [fam-] trastuzumab deruxtecan among 111 evaluable patients with HER2-positive metastatic breast cancer.

Both trials showed similar safety and tolerability profiles. The most common adverse events included nausea, decreased appetite, vomiting, alopecia, fatigue, anemia, diarrhea and constipation. Drug-related interstitial lung disease and pneumonitis, including grade 5 events, also have occurred.

“[Fam-] trastuzumab deruxtecan has the potential to transform the treatment landscape for patients with HER2-positive metastatic breast cancer who have limited treatment options,” José Baselga, MD, PhD, executive vice president of research and development oncology at AstraZeneca, said in the release. “The priority review draws on the strength and consistency of results seen in phase 1 and phase 2 trials and is an important step on the journey to deliver this potential new medicine to patients.”