durvalumab

Overview

Durvalumab is a human monoclonal antibody that targets Programmed Death-Ligand 1 (PD-L1), a protein that plays a crucial role in the immune system's ability to recognize and attack cancer cells. By inhibiting the interaction between PD-L1 and its receptor, programmed cell death protein 1 (PD-1), durvalumab enhances T-cell activation and proliferation, thereby promoting an anti-tumor immune response. This mechanism positions durvalumab as a significant player in cancer immunotherapy, particularly in the treatment of various malignancies, including non-small cell lung cancer (NSCLC), bladder cancer, and hepatocellular carcinoma (HCC).

Focus of Latest Publications

Recent publications have investigated durvalumab-based combinations across multiple cancer types and treatment settings. In hepatocellular carcinoma, durvalumab continues to be studied extensively. The STRIDE regimen combining tremelimumab and durvalumab improved survival in unresectable HCC, with pretreatment intratumoral CD8+ tumor-infiltrating lymphocyte density emerging as a biomarker associated with treatment response and progression-free survival. The HILL trial examined triple-combination therapy pairing durvalumab with lenvatinib and hepatic arterial infusion chemotherapy using FOLFOX in unresectable HCC, demonstrating a median progression-free survival of 15.8 months and objective response rate of 75.0% with a favorable safety profile. Additional studies evaluated durvalumab plus gemcitabine-cisplatin, second-line durvalumab plus tremelimumab versus lenvatinib following first-line atezolizumab plus bevacizumab, temporal survival dynamics comparing these regimens, and real-world safety and hepatic function preservation during STRIDE treatment.

Durvalumab demonstrated sustained activity in early-stage solid tumors when integrated into neoadjuvant and perioperative treatment strategies. The GeparNuevo trial revealed that adding durvalumab to neoadjuvant chemotherapy in early triple-negative breast cancer sustained significant long-term survival benefits compared to placebo, with improvements in invasive disease-free survival (hazard ratio 0.56), distant disease-free survival (hazard ratio 0.41), and overall survival (hazard ratio 0.33) that persisted irrespective of pathologic response. The NIAGARA trial resulted in FDA approval of neoadjuvant durvalumab combined with gemcitabine and cisplatin, followed by adjuvant durvalumab, for muscle-invasive bladder cancer, demonstrating significant improvements in event-free survival (hazard ratio 0.68) and overall survival (hazard ratio 0.75). The MATTERHORN trial showed that perioperative durvalumab combined with FLOT significantly improved event-free survival and overall survival in gastric and gastroesophageal junction cancer.

In advanced and metastatic malignancies, durvalumab combined with chemotherapy, targeted therapy, or radiation demonstrated clinically meaningful activity across multiple tumor types. The DUO-E trial in advanced endometrial cancer demonstrated that chemotherapy plus durvalumab followed by maintenance durvalumab or durvalumab plus olaparib reduced disease progression or death compared with chemotherapy alone, with greatest benefit in mismatch repair deficient tumors and additional benefit from olaparib in mismatch repair proficient disease. A phase II study of olaparib plus durvalumab in metastatic castration-resistant prostate cancer reported median overall survival of 19.1 months, with enriched benefit in BRCA2-variant disease and correlation between baseline cell-free tumor DNA fraction and clinical outcomes. In non-small cell lung cancer, durvalumab was evaluated in combination with chemotherapy and stereotactic ablation body radiotherapy for oligometastatic disease, with chemotherapy plus durvalumab in early-stage operable N2+ disease in the CHIO3 trial, and in combination with the ATR kinase inhibitor ceralasertib in previously treated advanced/metastatic patients.

Additional investigations expanded durvalumab's therapeutic applications and identified predictive biomarkers. A prospective phase 2 trial examined concurrent administration of durvalumab with chemoradiotherapy in limited-stage small cell lung cancer as an alternative to conventional post-treatment consolidation immunotherapy. In biliary tract carcinoma, the albumin-bilirubin score emerged as a prognostic predictor of outcomes with durvalumab plus gemcitabine-cisplatin. Mechanistic studies in gallbladder cancer identified the ERRα-ETV5-PD-L1 signaling axis as a driver of immune evasion, demonstrating that combined targeting of ERRα and durvalumab synergistically suppressed tumor growth and enhanced intratumoral T cell infiltration in preclinical and humanized mouse models.