Datopotamab deruxtecan

Dato-DXd plus durvalumab achieved a 50% overall pathologic complete response (pCR) rate in stage II/III high-risk HER2-negative breast cancer patients, according to the I-SPY 2.2 trial. The study highlights the utility of evaluating treatment response by response predictive subtype (RPS), with further investigation needed in immune-positive and hormone receptor–negative/DNA damage repair deficiency–negative subtypes. The combination showed promising results in the immune-positive and triple-negative subtypes, with over 50% of pCRs achieved by the end of block A, avoiding standard chemotherapy.

Durvalumab combined with datopotamab deruxtecan showed highest pathologic complete response rates in NeoCOAST-2 trial for resectable NSCLC, with 34.1% in arm 4, and a favorable safety profile.

Post-hoc analysis in DESTINY-Breast12 showed CNS ORR of 82.6% in patients without prior CNS therapy and 50.0% in those with prior therapy. Safety profiles of Enhertu were consistent with previous trials, with no new concerns. ILD/pneumonitis rates were 12.9% and 16.0% in patients without and with brain metastases, respectively, with most events being low grade.

DESTINY-Breast12 study highlights T-DXd's efficacy in HER2+ mBC patients with brain metastases, showing a 12-month PFS rate of 61.6% and varying ORR based on BM status. Tucatinib remains preferred for active BMs, but T-DXd demonstrates promising CNS activity. Safety profile aligns with previous reports, with ILD/pneumonitis as a key risk. T-DXd supports treatment for HER2+ mBC, including stable and active BMs.

AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan showed a 2.3-month survival advantage in nonsquamous non-small cell lung cancer patients, but lacked statistical significance. FDA approval by Dec. 20 is uncertain, with a potential advisory committee meeting. The drug, an antibody-drug conjugate, aims to replace chemotherapy but faces complexities in identifying responders.

Datopotamab deruxtecan (Dato-DXd) showed no statistically significant overall survival improvement in phase III TROPION-Lung01 trial for advanced or metastatic NSCLC, except in non-squamous NSCLC subgroup. AstraZeneca and Daiichi Sankyo focus on this subgroup, highlighting potential role of Dato-DXd in non-small cell lung cancer.

TROPION-Lung01 trial results show datopotamab deruxtecan improves overall survival (OS) over docetaxel in nonsquamous NSCLC patients, with a mean OS improvement of 2.3 months. Developed by Daiichi Sankyo and AstraZeneca, the TROP2-directed ADC is under review for marketing authorisation in NSCLC and HER2-negative breast cancer. The NSCLC market is projected to grow to $45.4bn by 2031, with datopotamab deruxtecan estimated to generate $6bn in annual global sales by 2030.

AstraZeneca’s QCS platform improved responses to Dato-DXd in NSCLC, particularly in nonsquamous NSCLC, reducing disease progression by 43%. QCS identified patients likely to benefit from Dato-DXd, with 66% of nonsquamous NSCLC patients being TROP2-QCS biomarker-positive. Median PFS was 6.9 months for Dato-DXd vs. 2.9 months for docetaxel in TROP2-QCS biomarker-positive patients.

AstraZeneca and Daiichi Sankyo's Phase III TROPION-Lung01 study showed datopotamab deruxtecan (Dato-DXd) failed to significantly improve overall survival in non-small cell lung cancer patients, with a 6% drop in death risk and 16% OS benefit in non-squamous NSCLC, both missing statistical significance. Despite this, AstraZeneca remains confident in Dato-DXd's potential role in lung cancer treatment.

AstraZeneca shares dropped 5% after disappointing lung cancer drug trial results, with its experimental drug datopotamab deruxtecan not significantly improving overall survival for patients.