AstraZeneca and Daiichi Sankyo's investigational antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) has faced challenges in two pivotal Phase 3 cancer trials. However, the partners remain steadfast in their commitment to further developing this promising therapy, as demonstrated by their ongoing clinical trials evaluating Dato-DXd across various indications.

TROPION-Breast01: Insights for Future Progress

In the TROPION-Breast01 study, Dato-DXd was evaluated against physicians' choice of chemotherapy for previously treated metastatic breast cancer patients whose tumors were hormone receptor (HR)-positive and HER2-low or negative. Although the drug had previously met the progression-free survival (PFS) goal, it did not achieve statistical significance in the final overall survival (OS) endpoint.

AstraZeneca attributed this outcome to other ADCs, like Enhertu, that became available during the trial, which likely impacted survival outcomes after disease progression. While the OS results fell short of statistical significance, the partners view the results as clinically meaningful and favoring Dato-DXd.

Notably, Dato-DXd demonstrated promising efficacy signals. In TROPION-Breast01, Dato-DXd significantly improved PFS by nearly 2 months versus chemotherapy. AstraZeneca and Daiichi plan to leverage the totality of evidence, including favorable safety and tolerability profiles, in discussions with health authorities regarding Dato-DXd's regulatory path for this indication. Analysts have previously projected Dato-DXd's potential to reach $9.4 billion in global peak sales, underscoring the therapy's significant potential impact.

TROPION-Lung01: Encouraging Signs and Ongoing Evaluation

In the TROPION-Lung01 trial for advanced non-small cell lung cancer (NSCLC), Dato-DXd demonstrated a numerical but non-significant 2.3-month OS improvement over standard-of-care docetaxel chemotherapy in a pre-specified subgroup analysis of patients with nonsquamous NSCLC.

While the OS improvement did not reach statistical significance, Dato-DXd achieved the PFS endpoint in the overall trial population. The partners have shared these data with regulators, as Dato-DXd is currently under review by the FDA for the treatment of NSCLC, with a regulatory decision anticipated in early 2025.

Ongoing Commitment to Dato-DXd's Development

Despite the recent challenges, AstraZeneca and Daiichi remain dedicated to further developing Dato-DXd, as evidenced by their ongoing Phase 3 clinical trials evaluating the drug across various other breast cancer indications, including TROPION-Breast02, TROPION-Breast03, TROPION-Breast04, and TROPION-Breast05.