Datopotamab deruxtecan

TROPION-Breast01 phase 3 trial of datopotamab deruxtecan (Dato-DXd) did not achieve statistical significance in overall survival (OS) analysis for inoperable or metastatic hormone receptor (HR) positive, HER2 low or negative breast cancer patients, despite meeting progression-free survival (PFS) primary endpoint.

TROPION-Breast01 Phase III trial of datopotamab deruxtecan did not achieve statistical significance in overall survival (OS) analysis for inoperable or metastatic HR-positive, HER2-low or negative breast cancer patients, despite meeting progression-free survival (PFS) primary endpoint. Safety profile consistent with previous analysis, with no new safety concerns. Multiple ADCs approved during trial likely affected survival results. AstraZeneca and Daiichi Sankyo continue discussions with regulatory authorities and clinical development for datopotamab deruxtecan.

Final overall survival results from TROPION-Breast01 Phase III trial of datopotamab deruxtecan (Dato-DXd) did not achieve statistical significance in HR-positive, HER2-low or negative breast cancer patients, despite positive progression-free survival results. Safety profile remained consistent with no new concerns. Subsequent treatment options likely affected survival results.

Dato-DXd plus durvalumab achieved a 50% 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 emphasizes evaluating treatment response per response predictive subtype (RPS) and suggests further investigation in immune-positive and hormone receptor (HR)-negative/DNA damage repair deficiency (DRD)-negative subtypes. The combination's efficacy was supported by the BEGONIA trial, showing a 79% objective response rate in metastatic triple-negative breast cancer. The I-SPY 2.2 trial design uses RPS to optimize drug assignment, aiming to improve efficacy and minimize toxicity.

The global ADC market is rapidly expanding, driven by increasing demand for targeted therapies. Over 15 ADCs are approved, with more than 600 in clinical trials. At least 10 new approvals are expected in the next couple of years. Numerous ADC candidates are in pivotal stages, with over 20 in Phase 3 trials. Key drugs in late-stage trials include Ifinatamab deruxtecan, DP 303c, BL B01D1, 9MW 2821, Telisotuzumab vedotin, and Datopotamab deruxtecan.

TROPION-PanTumor03 study results show datopotamab deruxtecan (Dato-DXd) has notable antitumor efficacy and a tolerable safety profile in advanced ovarian and endometrial cancers post-platinum chemotherapy. The objective response rate (ORR) was 42.9% in ovarian and 27.5% in endometrial cancers. The study also highlighted differences in patient characteristics and treatment outcomes between the two cohorts.

Datopotamab deruxtecan (Dato-DXd) showed antitumor activity in advanced/metastatic ovarian and endometrial cancer patients post-platinum chemotherapy, with ORR of 42.9% in ovarian and 27.5% in endometrial cancer. The study, TROPION-PanTumor03, also highlighted tolerable side effects and no TEAE-related deaths.

Merck and Daiichi Sankyo's patritumab deruxtecan met primary endpoint in Phase III HERTHENA-Lung02 study for EGFR-mutated non-small cell lung cancer, showing significant improvement in progression-free survival. Safety profile consistent with prior studies, though two grade 5 interstitial lung disease deaths occurred. Full results to be presented at a medical meeting.

Dato-DXd plus durvalumab achieved a 50% overall pathologic complete response (pCR) rate in stage II/III high-risk HER2-negative breast cancer patients, highlighting the utility of response predictive subtype (RPS) evaluation. The I-SPY 2.2 trial's findings suggest further investigation in immune-positive and hormone receptor (HR)-negative/DNA damage repair deficiency (DRD)-negative subtypes is warranted.

Dr. Begona Perez-Valderrama discussed novel agents and combinations in RCC and urothelial carcinoma at the 2024 ESMO meeting, highlighting belzutifan's potential in RCC therapy and ongoing trials assessing various combinations, including antibody-drug conjugates like disitamab vedotin and trastuzumab deruxtecan.