Datopotamab deruxtecan

AstraZeneca and Daiichi Sankyo shares fell due to mixed results in a late-stage trial for their lung cancer drug Dato-DXd, which showed some patients lived longer but overall results were not statistically significant. The drug is expected to be approved based on overall survival and progression-free survival improvements.

TROP2 protein in NSCLC predicts better outcomes with datopotamab deruxtecan (dato-DXd) vs. docetaxel, per TROPION-Lung01 trial analysis. Dato-DXd reduced progression risk by 43% in TROP2-QCS biomarker-positive patients vs. 25% overall, with no new safety concerns. AstraZeneca and Roche Tissue Diagnostics plan to co-develop a TROP2-QCS biomarker companion diagnostic.

TROPION-Lung01 trial results show datopotamab deruxtecan (12.9 months OS) vs. docetaxel (11.8 months OS) in overall population, with nonsquamous histology showing 14.6 months vs. 12.3 months OS. In patients with actionable genomic alterations, datopotamab deruxtecan showed 15.6 months OS compared to 9.8 months with docetaxel. NeoCOAST-2 trial preliminary results indicate 34.1% pCR and 65.9% mPR with datopotamab deruxtecan plus Imfinzi and carboplatin in early-stage NSCLC.

Datopotamab deruxtecan showed a median overall survival of 14.6 months in patients with advanced nonsquamous non-small cell lung cancer in the TROPION-Lung01 Phase III trial. The trial, evaluating AstraZeneca and Daiichi Sankyo's drug versus chemotherapy, met the dual primary endpoint of progression-free survival. Results were presented at the IASLC 2024 World Conference on Lung Cancer.

IMFINZI is indicated for various lung cancer treatments, including unresectable Stage III NSCLC, metastatic NSCLC, extensive-stage SCLC, and biliary tract cancer. It also treats unresectable HCC in combination with IMJUDO. TROPION-Lung01 and NeoCOAST-2 are Phase III and II trials evaluating datopotamab deruxtecan and IMFINZI, respectively, in lung cancer. AstraZeneca collaborates with Daiichi Sankyo for ADC development and aims to improve lung cancer outcomes.

Adding novel agents to perioperative durvalumab for NSCLC led to higher pCR and mPR rates compared to historical rates with durvalumab and chemotherapy. The highest response rates occurred with the addition of Dato-DXd (pCR 34.1%, mPR 65.9%). All combinations demonstrated manageable safety profiles and surgical rates comparable to approved regimens.

AstraZeneca and Daiichi Sankyo unveiled an AI-powered TROP2-QCS biomarker predicting clinical outcomes in NSCLC patients treated with datopotamab deruxtecan. In TROPION-Lung01 Phase III study, TROP2-QCS-positive patients showed a 43% reduction in disease progression or death risk with Dato-DXd vs. docetaxel, compared to 25% in the overall study population. TROP2-QCS, developed via AstraZeneca’s QCS platform, assesses TROP2 membrane expression relative to cytoplasm, classifying patients as TROP2-QCS-positive if 75% of tumor cells have an NMR below a specified value.

TROPION-Lung01 Phase III trial results show datopotamab deruxtecan (6.0mg/kg) had a median OS of 12.9 months vs. 11.8 months for docetaxel (75mg/m²) in advanced NSCLC patients. The HR was 0.94 (95% CI 0.78-1.14), with a p-value of 0.530. In nonsquamous histology, datopotamab deruxtecan showed a median OS of 14.6 months vs. 12.3 months for docetaxel, with an HR of 0.84 (95% CI 0.68-1.05). Patients with actionable genomic alterations saw a median OS of 15.6 months with datopotamab deruxtecan vs. 9.8 months with docetaxel, HR 0.65 (95% CI 0.40-1.08). NeoCOAST-2 trial showed datopotamab deruxtecan plus Imfinzi and carboplatin had a pCR rate of 34.1% and mPR rate of 65.9% in early-stage resectable NSCLC.

Innate Pharma announced AstraZeneca's interim NeoCOAST-2 Phase 2 study results at the 2024 World Conference on Lung Cancer, showing promising efficacy and safety profiles for monalizumab in early-stage NSCLC.