durvalumab + vactosertib

The combination of durvalumab and vactosertib is being investigated as a potential therapeutic approach for various cancers. This combination pairs **durvalumab**, an anti-PD-L1 monoclonal antibody, with **vactosertib**, a TGF-β type I receptor kinase inhibitor. ## Clinical Development The combination has shown promising results in clinical trials, demonstrating a manageable safety profile and encouraging anti-tumor activity. Clinical trials have investigated this combination for several cancer types: 1. **Advanced Non-Small Cell Lung Cancer (NSCLC)**: A Phase 1b/2a open-label study assessed the safety, tolerability, pharmacokinetics, and antitumor activity of vactosertib in combination with durvalumab in patients with advanced NSCLC who progressed following platinum-based chemotherapy. 2. **Metastatic Gastric Cancer**: A Phase 2 trial is testing the efficacy and safety of durvalumab in combination with vactosertib in patients with metastatic gastric cancers who failed ≥2 lines of chemotherapy. 3. **Urothelial Carcinoma**: A Phase 2, open-label, non-randomized single-arm study is evaluating whether the administration of vactosertib with durvalumab will provide meaningful clinical benefit in patients with urothelial carcinoma. ## Safety Profile The combination has demonstrated a manageable safety profile in clinical trials: - Most adverse events were grade 1 or 2 and generally manageable. - In studies, the combination showed dose-limiting toxicities were limited following oral administration of vactosertib at all dose levels tested. - The maximum tolerated dose (MTD) for vactosertib was determined to be 200 mg po bid in some studies. ## Mechanism of Action This combination represents a strategic approach to cancer treatment by targeting two important pathways: 1. **Durvalumab**: An anti-PD-L1 monoclonal antibody that blocks the interaction between PD-L1 and its receptors, enhancing T-cell responses and anti-tumor immunity. 2. **Vactosertib**: A selective TGF-β type I receptor kinase inhibitor that blocks TGF-β signaling, which is often associated with immunosuppression and tumor progression. The rationale behind this combination is that blocking TGF-β signaling with vactosertib may enhance the efficacy of immunotherapy with durvalumab by reducing immunosuppression in the tumor microenvironment. ## Administration In clinical trials, the combination has been administered as follows: - Durvalumab: Intravenous (IV) infusion every 4 weeks (Q4W) - Vactosertib: Oral (PO) twice daily (bid) for 5 days a week for up to a maximum of 12 months. This combination represents an innovative approach to cancer treatment by simultaneously targeting immune checkpoint inhibition and TGF-β signaling pathways.

Brand names

Imfinzi

Other names

durvalumab and vactosertib