Despite the disappointing late-stage results in non-small cell lung cancer, Jefferies analyst Stephen Barker contends the likelihood of FDA approval “remains high” for the experimental antibody-drug conjugate, though the regulator is now more likely to convene an advisory committee.
AstraZeneca and Daiichi Sankyo on Monday revealed detailed findings from the Phase III TROPION-Lung01 study, showing that their investigational antibody-drug conjugate datopotamab deruxtecan failed to significantly improve overall survival in certain patients with non-small cell lung cancer.
Patients on datopotamab deruxtecan (Dato-DXd) achieved mean overall survival (OS) of 12.9 months, versus 11.8 months in those treated with the chemotherapy drug docetaxel. This difference corresponded to a 6% drop in the risk of death, which was in favor of Dato-DXd but fell short of statistical significance, according to AstraZeneca.
In the subset of patients with non-squamous non-small cell lung cancer (NSCLC), Dato-DXd’s OS benefit of 16% also missed statistical significance, though this nominal improvement held up regardless of patients’ genetic mutation status.
Despite Monday’s disappointing data, Susan Galbraith, AstraZeneca’s executive vice president of oncology R&D, struck a positive note in a statement, noting that Dato-DXd still “showed a clinically meaningful trend towards improving the survival” of non-squamous NSCLC patients with advanced or metastatic disease.
“These results underscore our confidence in the important role datopotamab deruxtecan can play across segments and settings of non-small cell lung cancer,” Galbraith said.
AstraZeneca presented these findings during an oral session at the 2024 World Congress on Lung Cancer of the International Association for the Study of Lung Cancer (IASLC) and simultaneously published the data in the Journal of Clinical Oncology.
AstraZeneca and Daiichi Sankyo previously reported disappointing OS data for Dato-DXd. The partners revealed in May 2024 that Dato-DXd yielded no significant OS benefit for NSCLC patients. At the time, however, the companies touted their non-squamous data, which provided encouraging signals.
At an interim readout in October 2023, Dato-DXd resulted in a 23% improvement in OS, an effect that slightly missed statistical significance.
In a note to investors, Jefferies analyst Stephen Barker called this drop in Dato-DXd’s OS estimate “disappointing,” with its hazard ratio worsening “from 0.77 at interim to 0.84” on Monday. “Because the upper end of the [confidence intervals] exceeds 1, it is not possible to claim with 95% certainty that the observed benefit is not the result of chance,” Barker wrote, referring to Dato-DXd’s trend toward longer patient survival.
Still, Barker contends that Dato-DXd’s likelihood of approval “remains high,” though the FDA is now more likely to convene an advisory committee ahead of its target action date. AstraZeneca and Daiichi Sankyo have filed for non-squamous NSCLC approval for their antibody-drug conjugate, with a PDUFA date of Dec. 20, 2024.
