DAIICHI SANKYO, INC.

AstraZeneca has a broad development program for GI cancers, focusing on gastric, liver, biliary tract, oesophageal, pancreatic, and colorectal cancers. Key treatments include Imfinzi, Enhertu, Lynparza, and novel modalities targeting Claudin 18.2 and Glypican 3. The company is also a pioneer in immuno-oncology, aiming to redefine cancer care with innovative therapies and combinations. AstraZeneca's oncology ambition is to provide cures for all forms of cancer.

Early switch to atezolizumab after vemurafenib plus cobimetinib in BRAF V600-positive melanoma showed improved OS at 4 and 5 years in the ImmunoCobiVem trial, but not statistically significant. Rapid progression after switch to immune checkpoint inhibition was observed in some patients.

Enhertu demonstrated superior efficacy in treating HER2+ breast cancer brain metastases at ESMO 2024, outperforming Kadcyla. Enhertu's 12-month PFS was 61.6% with an ORR of 79% for CNS metastases, maintaining 90.3% OS in active BCBM patients. Analysts predict Enhertu will dominate the ADC market, reaching $11.2bn by 2030, while Kadcyla and Tukysa are projected to achieve $838m and $1.2bn respectively.

Initial results from Daiichi Sankyo’s phase 1 trial of DS-9606, a CLDN6-directed ADC, show promising clinical activity in advanced solid tumors expressing CLDN6, with no dose-limiting toxicities observed.

Preoperative chemoradiotherapy did not improve survival over perioperative chemotherapy alone in resectable gastric and gastroesophageal junction adenocarcinoma, according to TOPGEAR data. Median overall survival was 46.4 months vs 49.4 months, with no significant differences in progression-free survival. However, preoperative chemoradiotherapy significantly improved pathological outcomes, including complete response rates and tumor downstaging.

R.A.S., M.S.T., C.Y., R.N., H.S.R., M.D., A.J.C., E.S.-R., J.C.B., C.O., K.K., A.D.E., C.V., N.W., K.S.A., A.S.C., C.F., C.I., A.T., J.T., K.Y., L.H., K.G., F.M.H., T.S., A.L.A., P.B., P.N., G.L.H., W.F.S., J.P., P.P., A.D.M., D.Y., L.J.v.V., N.M.H., L.J.E. report various institutional research funding, advisory roles, consultancy, honoraria, patents, and stock ownership.

Various researchers report financial relationships with pharmaceutical companies, including Deciphera, during and outside the conduct of the study.

Dr. Barbara Pistilli presents encouraging phase II ICARUS-BREAST01 results for patritumab deruxtecan, a new antibody-drug conjugate for metastatic breast cancer, showing a 53.5% response rate and 9.4 months median progression-free survival. The study identifies factors influencing response, suggesting potential as a new therapy for advanced hormone-dependent breast cancer.

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.

Datopotamab failed to significantly increase overall survival in a Phase III study for non-small cell lung cancer, but a new biomarker and encouraging data in a subset of patients highlight the potential of precision medicine.