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.

Key Publications

• NEWJul Pretreatment Tumor-infiltrating CD8+ T Cell Numbers Are Associated With the Response to Tremelimumab Plus Durvalumab in Hepatocellular Carcinoma. (Anticancer research, 2026, PMID 42373240): "The STRIDE regimen, combining tremelimumab and durvalumab, improves the survival of patients with unresectable HCC, but a substantial proportion of patients experience early progression."
• May HILL: the efficacy and safety of hepatic arterial infusion chemotherapy with the FOLFOX regimen combined with lenvatinib and the PD-L1 inhibitor durvalumab in unresectable hepatocellular carcinoma: a prospective, single-arm, phase 2 clinical trial. (Signal transduction and targeted therapy, 2026, PMID 42135293): "This study aimed to evaluate the efficacy and safety of combining hepatic arterial infusion chemotherapy with FOLFOX (FOLFOX-HAIC), lenvatinib, and the PD-L1 inhibitor durvalumab in this population, with all uHCC patients receiving the triple-combination regimen as initial therapy."
• May The Albumin-Bilirubin score predicts outcomes in advanced biliary tract cancer treated with durvalumab immunochemotherapy. (The oncologist, 2026, PMID 42095607): "its prognostic value in patients with biliary tract carcinoma (BTC) treated with durvalumab plus gemcitabine-cisplatin (GCD) remains unclear."
• May Comparison of outcomes of second-line durvalumab plus tremelimumab versus lenvatinib following first-line atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. (PloS one, 2026, PMID 42096473): "In this study, we compared second-line durvalumab plus tremelimumab with lenvatinib after first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma (uHCC)."
• Jun Early and late survival dynamics of immunotherapy combinations in advanced HCC: Anchored indirect comparison of atezolizumab plus bevacizumab versus durvalumab + tremelimumab. (European journal of cancer (Oxford, England : 1990), 2026, PMID 42068971): "Atezolizumab plus bevacizumab (A+B) and STRIDE (tremelimumab plus durvalumab) represent two of the approved first-line immunotherapy strategies for unresectable hepatocellular carcinoma (HCC)."
• Jun Durvalumab in Combination With Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: Long-Term Analysis From the GeparNuevo Trial. (Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2026, PMID 42008768): "The phase II GeparNuevo trial investigated whether adding durvalumab to neoadjuvant chemotherapy (NACT) only in patients with early triple-negative breast cancer cT1b-cT4a-d would improve pathologic complete response (pCR) rate and patient survival."
• May Durvalumab-Tremelimumab in Advanced Hepatocellular Carcinoma: Real-World Data From the LOR-HCC (Lombardy Real-World HCC Group). (Liver international : official journal of the International Association for the Study of the Liver, 2026, PMID 41992826): "Dual immune checkpoint blockade with tremelimumab plus durvalumab (STRIDE) is an established first-line therapy for unresectable hepatocellular carcinoma (uHCC);"
• Apr Practice-Changing Trials in Gastrointestinal Cancers at ASCO 2025: A Critical Review and Clinical Context. (Cancer investigation, 2026, PMID 41960736): "MATTERHORN demonstrated significant improvements in event-free survival and OS with perioperative durvalumab plus FLOT in gastric/GEJ cancer."
• Apr Plain language summary of results from the DUO-E study: durvalumab given with or without olaparib in patients with advanced endometrial cancer. (Future oncology (London, England), 2026, PMID 41943281): "The DUO-E study is testing an immunotherapy, durvalumab, and a targeted therapy, olaparib, in people with newly diagnosed advanced endometrial cancer or recurrent endometrial cancer."
• Jun Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC. (British journal of cancer, 2026, PMID 41917211): "This multicentre, modular, Phase 1 study evaluated escalating doses of ATR (ataxia telangiectasia and Rad3-related kinase) inhibitor ceralasertib plus PD-L1 inhibitor durvalumab in patients with previously treated advanced/metastatic non-small-cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (HNSCC)."