Datroway (datopotamab deruxtecan-dlnk)

P3, N=625, Recruiting, AstraZeneca | Trial completion date: Apr 2029 --> Sep 2030 | Trial primary completion date: Oct 2026 --> Jul 2027

P3, N=1170, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting

The success of inhibitors like sotorasib and adagrasib has expanded options for targeting once 'undruggable' oncogenic drivers such as KRAS...ADCs such as EMRELIS™, Datroway, and ELAHERE™ offer precise targeting along with potent cytotoxic agents...Cancer vaccine research is progressing with licensed immunoprophylactic drugs, and AI tools like AlphaFold are speeding up drug discovery by enhancing structural biology predictions. This review covers recent cancer therapeutics advancements, including targeted inhibitors, immunotherapies, resistance strategies, epigenetic interventions, combination therapies, vaccines, and AI applications.

P3, N=744, Recruiting, AstraZeneca | Active, not recruiting --> Recruiting

The addition of osimertinib to curative-intent strategies have demonstrated improvements in disease-free survival and overall survival (OS) as adjuvant therapy in resected stage IB-IIIa patients, major pathological responses compared to chemotherapy when used as neoadjuvant therapy, and progression-free survival (PFS) compared to placebo when used as consolidation therapy in unresectable stage III patients. Currently, subsequent treatment recommendations include chemotherapy or datopotamab deruxtecan following progression on a third-generation EGFR-TKI combination and amivantamab plus platinum-based chemotherapy following progression on monotherapy. The treatment landscape for NSCLC with common EGFR mutations is rapidly evolving and third-generation EGFR-TKIs play an integral role in both the curative-intent and palliative settings.

Data from this study could lead to a new treatment option in this setting. ClinicalTrials.gov identifier: NCT06417814 (date of registration: May 13, 2024).

Dato-DXd demonstrates encouraging antitumor activity and a manageable safety profile in several advanced solid tumors, particularly breast cancer and NSCLC. This synthesis provides a valuable evidence base to guide clinical practice and future trial design. However, as the current evidence is predominantly from early phase and single-arm studies, confirmation through large-scale randomized controlled trials is necessary before Dato-DXd can be widely adopted in clinical practice.

TROPION-Breast01 met its dual primary endpoint of PFS by BICR. While there was no statistically significant improvement in the dual primary endpoint of OS with Dato-DXd versus ICC, subsequent ADC treatment may have affected OS results. The totality of efficacy and safety data support Dato-DXd as a new treatment option for patients with previously treated, inoperable/metastatic HR+/HER2‒ breast cancer.

TROP-2-directed ADCs demonstrate meaningful efficacy in previously treated advanced NSCLC, especially among EGFR-mutant and non-squamous histology patients, with survival and response outcomes superior to traditional chemotherapy. However, high rates of adverse events, particularly ILD, necessitate close monitoring. Further randomized and biomarker-driven studies are warranted to refine patient selection and optimize the therapeutic potential of these agents.

P3, N=400, Recruiting, AstraZeneca

This review summarizes a range of ADCs targeting tumor-associated antigens in ovarian cancer, including mirvetuximab soravtansine (MIRV), trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), sacituzumab tirumotecan (SKB-264), PF-06664178, anetumab ravtansine (BAY 94-9343), BMS-986148, DMOT4039A, RC88, lifastuzumab vedotin (DNIB0600A), upifitamab rilsodotin (ABBV-181), ZW220, DMUC4064A, and sofituzumab vedotin (DMUC5754A). The ADCs hold significant potential to reshape the treatment landscape for ovarian cancer by providing targeted therapeutic options. Further research is required to optimize patient selection, address resistance mechanisms, and improve safety profiles.

P3, N=744, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial completion date: May 2028 --> Sep 2028 | Trial primary completion date: Jun 2026 --> Sep 2026