AstraZeneca and Daiichi Sankyo's Dato-DXd Fails to Improve NSCLC Survival in Phase III

Despite underwhelming late-stage trial outcomes in non-small cell lung cancer, Jefferies analyst Stephen Barker remains optimistic about the likelihood of FDA approval for the experimental antibody-drug conjugate, datopotamab deruxtecan (Dato-DXd). However, he suggests that an advisory committee may be convened by the regulator.

AstraZeneca and Daiichi Sankyo shared detailed results from the Phase III TROPION-Lung01 study on Monday. The study revealed that Dato-DXd failed to show a statistically significant improvement in overall survival (OS) compared to the chemotherapy drug docetaxel in certain patients with non-small cell lung cancer. Specifically, patients treated with Dato-DXd had an average OS of 12.9 months, slightly better than the 11.8 months for those on docetaxel. This resulted in a 6% reduction in the risk of death, favoring Dato-DXd, but it was not statistically significant, according to AstraZeneca.

In a specific group of patients with non-squamous non-small cell lung cancer (NSCLC), Dato-DXd showed a 16% improvement in OS. However, this improvement also did not reach statistical significance, though it was consistent regardless of the patients’ genetic mutations.

Despite these disappointing results, Susan Galbraith, AstraZeneca’s executive vice president of oncology R&D, remained optimistic. She highlighted that Dato-DXd exhibited a “clinically meaningful trend towards improving the survival” of patients with advanced or metastatic non-squamous NSCLC. She emphasized the potential important role that datopotamab deruxtecan could play in various segments and settings of non-small cell lung cancer. 

The findings were presented by AstraZeneca during an oral session at the 2024 World Congress on Lung Cancer hosted by the International Association for the Study of Lung Cancer (IASLC). The data was also published in the Journal of Clinical Oncology.

This isn't the first time AstraZeneca and Daiichi Sankyo have faced setbacks with Dato-DXd. In May 2024, the companies reported that Dato-DXd did not show a significant OS benefit for NSCLC patients. However, they highlighted encouraging signals from the non-squamous subgroup data. During an interim analysis in October 2023, Dato-DXd demonstrated a 23% improvement in OS, although this also narrowly missed statistical significance.

Jefferies analyst Stephen Barker addressed this decline, noting that Dato-DXd’s OS estimate had worsened, with its hazard ratio deteriorating from 0.77 at interim analysis to 0.84 in the latest results. He indicated that because the upper end of the confidence intervals exceeded 1, it is impossible to assert with 95% certainty that the observed benefit was not due to chance. Nonetheless, Barker remains confident that the likelihood of Dato-DXd's approval is high, although the FDA may now be more inclined to convene an advisory committee before its target action date.

AstraZeneca and Daiichi Sankyo have already submitted a filing for the approval of Dato-DXd for non-squamous NSCLC, with a Prescription Drug User Fee Act (PDUFA) date set for December 20, 2024.

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