{ "id": "ephgvp0ex3", "slug": "durvalumab-and-tremelimumab-regimen", "title": "Durvalumab and tremelimumab regimen", "updated": "2026-10-15", "topic_path": [ { "id": "life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/topics/life" }, { "id": "life.health", "label": "Human health and medicine", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health" }, { "id": "life.health.medicines", "label": "Medicines and therapeutics", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.medicines" }, { "id": "life.health.medicines.biologics-mabs", "label": "Biologics, monoclonal antibodies, and biosimilars", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.medicines.biologics-mabs" } ], "geo": [ { "id": "geo.nongeo.t2001.life.health.medicines", "label": "Non-geographic · 2001 to 2020: Medicines and therapeutics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t2001.life.health.medicines", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.t2001", "label": "Non-geographic · 2001 to 2020", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t2001" }, { "id": "geo.nongeo.t2001.life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t2001.life" }, { "id": "geo.nongeo.t2001.life.health", "label": "Human health and medicine", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t2001.life.health" }, { "id": "geo.nongeo.t2001.life.health.medicines", "label": "Medicines and therapeutics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t2001.life.health.medicines" } ] } ], "excerpt": "The durvalumab plus tremelimumab regimen, given as the STRIDE schedule of one tremelimumab dose plus regular durvalumab, is an approved immunotherapy for unresectable liver cancer and some lung cancers.", "snippet": "The durvalumab plus tremelimumab regimen, given as the STRIDE schedule of one tremelimumab dose plus regular durvalumab, is an approved immunotherapy for unresectable liver cancer and some lung cancers.", "node": "life.health.medicines.biologics-mabs", "markdown": "# Durvalumab and tremelimumab regimen\n\nThe durvalumab plus tremelimumab regimen is a combination cancer immunotherapy in which the anti-PD-L1 antibody durvalumab (Imfinzi) is given with the anti-CTLA-4 antibody tremelimumab (Imjudo), as the STRIDE schedule of one priming dose of tremelimumab followed by regular durvalumab. It is approved for unresectable hepatocellular carcinoma (HCC) and, with platinum-based chemotherapy, for metastatic non-small cell lung cancer (NSCLC) without sensitizing EGFR mutations or ALK aberrations.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10841291/) • [2](https://link.springer.com/article/10.1007/s11523-023-01026-9)\n\n| Key fact | Detail |\n|---|---|\n| Drugs | Durvalumab, human IgG1 anti-PD-L1; tremelimumab, human IgG2 anti-CTLA-4[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10841291/) |\n| HCC indication | Unresectable HCC, FDA approval October 21, 2022; EU authorization February 20, 2023[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10841291/) • [3](https://www.g-ba.de/downloads/91-1455-943/2024-10-08_Current-Version_Tremelimumab_D-924_EN.pdf) |\n| STRIDE schedule | Single 300 mg IV tremelimumab over 60 minutes plus durvalumab 1500 mg at cycle 1, then durvalumab 1500 mg every 4 weeks[2](https://link.springer.com/article/10.1007/s11523-023-01026-9) |\n| HCC survival benefit | Median OS 16.43 vs 13.77 months versus sorafenib (HR 0.78; P=0.0035); 36-month OS 30.7% vs 20.2%[4](https://pubmed.ncbi.nlm.nih.gov/38319892/) |\n| NSCLC regimen | Tremelimumab 75 mg plus durvalumab 1500 mg with chemotherapy every 3 weeks for 4 cycles, plus one tremelimumab dose at week 16[5](https://clinicaltrials.gov/study/NCT03164616) |\n| NSCLC survival benefit | Median OS 14.0 vs 11.7 months (HR 0.77) and PFS 6.2 vs 4.8 months (HR 0.72) versus chemotherapy alone[6](https://pubmed.ncbi.nlm.nih.gov/36327426/) |\n| Common adverse events | Rash 32%, diarrhea 27%, fatigue 26%, pruritus 23% in the HCC combination arm[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10841291/) |\n\n## How it works\n\nTremelimumab is a fully human IgG2 monoclonal antibody that blocks the interaction of CTLA-4 with its ligands CD80 and CD86 on antigen-presenting cells, releasing the brake on T-cell priming; in vitro it binds with more than 500-fold higher selectivity for CTLA-4 than for CD28, CD86, or IgG1.[2](https://link.springer.com/article/10.1007/s11523-023-01026-9) Durvalumab is a human IgG1 antibody that interferes with PD-L1 binding to PD-1, countering suppression of already-activated T cells within the tumor microenvironment.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10841291/) The mechanistic rationale is therefore complementary: CTLA-4 blockade initiates immune activation, while PD-L1 blockade sustains T-cell responses against the tumor.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12963680/)\n\nPharmacodynamic data support this sequence. In the phase I/II Study 22 in HCC, flow cytometry of peripheral blood collected on day 15 showed an increased number of proliferating T cells in the STRIDE arm compared with durvalumab monotherapy, and expansion of proliferating CD8+ lymphocytes was associated with objective responses.[8](https://aacrjournals.org/clincancerres/article/32/4/694/774475/T-Cell-Receptor-and-Immune-Gene-Expression)\n\n## How it is done\n\nFor unresectable HCC, the approved regimen is STRIDE (Single Tremelimumab Regular Interval Durvalumab): a single 300 mg tremelimumab dose by intravenous infusion over 60 minutes, followed by a separate durvalumab 1500 mg infusion at cycle 1/day 1, then durvalumab 1500 mg alone every 4 weeks until progression or unacceptable toxicity.[2](https://link.springer.com/article/10.1007/s11523-023-01026-9) For patients below 30 kg in the USA (below 40 kg in the EU), weight-based dosing applies, tremelimumab 4 mg/kg with durvalumab 20 mg/kg.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10841291/) • [2](https://link.springer.com/article/10.1007/s11523-023-01026-9)\n\nFor metastatic NSCLC, tremelimumab 75 mg plus durvalumab 1500 mg is given with platinum-based chemotherapy every 3 weeks for 4 cycles (weeks 0, 3, 6, and 9), then durvalumab every 4 weeks until progression, with one additional tremelimumab 75 mg dose at week 16.[5](https://clinicaltrials.gov/study/NCT03164616) • [6](https://pubmed.ncbi.nlm.nih.gov/36327426/) [Tremelimumab](https://www.edgepedia.org/tremelimumab) is infused first over 60 minutes, a 60-minute wait follows before durvalumab is infused over 60 minutes, and the drugs are not given through the same infusion line.[9](https://aimwithimmunotherapy.org/wp-content/uploads/2026/03/Tremelimumab-actl-HCP-Toolkit_120425-FINAL-1.pdf)\n\n## Origin\n\nThe combination entered clinical testing in a multicentre, open-label phase 1b study at five US cancer centers that enrolled 102 immunotherapy-naive patients with advanced NSCLC between October 28, 2013, and April 1, 2015.[10](https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2900544-6/abstract) [Durvalumab](https://www.edgepedia.org/durvalumab) 20 mg/kg every 4 weeks plus tremelimumab 1 mg/kg showed manageable tolerability and was selected as the dose for phase 3 studies.[10](https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2900544-6/abstract) The POSEIDON protocol was sponsored by AstraZeneca AB.[11](https://cdn.clinicaltrials.gov/large-docs/16/NCT03164616/Prot_002.pdf)\n\nIn HCC, the phase I/II randomized expansion (Study 22) tested durvalumab monotherapy, tremelimumab monotherapy, and combination schedules, including a novel regimen featuring a single priming dose of tremelimumab, the design that became STRIDE.[12](https://ascopubs.org/doi/10.1200/JCO.20.03555) Two phase 3 trials followed: POSEIDON (NCT03164616) in metastatic NSCLC and HIMALAYA (NCT03298451) in unresectable HCC.[5](https://clinicaltrials.gov/study/NCT03164616) • [13](https://clinicaltrials.gov/ct2/show/NCT03298451) On October 21, 2022, the FDA approved tremelimumab with durvalumab for adults with unresectable HCC,[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10841291/) and EU marketing authorization followed on February 20, 2023, for first-line advanced or unresectable HCC.[3](https://www.g-ba.de/downloads/91-1455-943/2024-10-08_Current-Version_Tremelimumab_D-924_EN.pdf)\n\n**HIMALAYA** randomized 1,171 patients to STRIDE (n=393), durvalumab monotherapy (n=389), or sorafenib 400 mg twice daily (n=389).[4](https://pubmed.ncbi.nlm.nih.gov/38319892/) Median overall survival was 16.43 months with STRIDE versus 13.77 months with sorafenib (HR 0.78; 96.02% CI 0.65 to 0.93; P=0.0035), and overall survival at 36 months was 30.7% versus 20.2%.[4](https://pubmed.ncbi.nlm.nih.gov/38319892/) Objective response rates were 20.1% with STRIDE and 5.1% with sorafenib.[14](https://ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.379) [Progression-free survival](https://www.edgepedia.org/progression-free-survival), however, was not prolonged (3.8 vs 4.1 months), so the benefit lies in long-term survival rather than delayed progression.[15](https://karger.com/lic/article/11/2/87/824981/Durvalumab-Plus-Tremelimumab-A-Novel-Combination)\n\n**POSEIDON** randomized 1,013 patients with EGFR/ALK wild-type metastatic NSCLC to tremelimumab plus durvalumab with chemotherapy (T+D+CT), durvalumab plus chemotherapy, or chemotherapy alone.[6](https://pubmed.ncbi.nlm.nih.gov/36327426/) T+D+CT improved overall survival (HR 0.77; median 14.0 vs 11.7 months; 24-month OS 32.9% vs 22.1%) and progression-free survival (HR 0.72; median 6.2 vs 4.8 months); the objective response rate was 39% versus 24%.[6](https://pubmed.ncbi.nlm.nih.gov/36327426/) • [9](https://aimwithimmunotherapy.org/wp-content/uploads/2026/03/Tremelimumab-actl-HCP-Toolkit_120425-FINAL-1.pdf) Durvalumab plus chemotherapy without tremelimumab improved PFS (HR 0.74) but its overall survival trend did not reach significance (HR 0.86; P=0.0758).[6](https://pubmed.ncbi.nlm.nih.gov/36327426/)\n\n## Variants\n\nIn HCC, EMERALD-3 tested STRIDE with or without lenvatinib plus transarterial chemoembolisation (TACE) in embolisation-eligible HCC.[16](https://www.bjmo.be/tremelimumab-and-durvalumab-with-or-without-lenvatinib-plus-transarterial-chemoembolisation-in-embolisation-eligible-hepatocellular-carcinoma-results-from-the-emerald-3-study/)\n\n## Applications\n\nThe combination with chemotherapy is approved for certain non-small cell lung cancers.[2](https://link.springer.com/article/10.1007/s11523-023-01026-9) A five-year POSEIDON update (median follow-up 63.4 months) showed sustained overall survival benefit for T+D+CT (HR 0.76; 5-year OS 15.7% vs 6.8%), with benefit regardless of PD-L1 expression, including tumor cell PD-L1 below 1%, and in STK11-mutant, KEAP1-mutant, and KRAS-mutant nonsquamous tumors; no new safety signals emerged.[17](https://europepmc.org/article/MED/39243945) An April 2026 sponsor release reported that durvalumab plus tremelimumab improved progression-free survival in early liver cancer, extending the program toward curative-intent disease.[18](https://business.am-news.com/am-news/article/bizwire-2026-4-2-imfinzi-durvalumab-imjudo-tremelimumab-actl-improves-pfs-in-early-liver-cancer)\n\n## Limitations and alternatives\n\nIn the HIMALAYA combination arm, the most common treatment-emergent adverse events above 20% were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), and abdominal pain (20%).[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC10841291/) Grade 3/4 events differ by how they are counted: 50.5% of STRIDE patients had grade 3/4 treatment-emergent adverse events in the NEJM report,[4](https://pubmed.ncbi.nlm.nih.gov/38319892/) while 25.8% had grade 3/4 treatment-related adverse events in the conference analysis, still lower than sorafenib (36.9%) and below the more than 50% reported for nivolumab plus ipilimumab in CheckMate 040; the single priming dose of anti-CTLA-4 is credited with this lower toxicity compared with conventional combination schedules.[14](https://ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.379) • [15](https://karger.com/lic/article/11/2/87/824981/Durvalumab-Plus-Tremelimumab-A-Novel-Combination) In POSEIDON, grade 3/4 treatment-related adverse events occurred in 51.8% (T+D+CT), 44.6% (D+CT), and 44.4% (chemotherapy) of patients.[6](https://pubmed.ncbi.nlm.nih.gov/36327426/) Real-world data show hepatitis as the most common toxicity (48% overall; 14% grade 3 or higher), with median overall survival of 14.0 months in the HIMALAYA-eligible subgroup.[19](https://www.techscience.com/or/v34n9/68350)\n\nAgainst alternatives, a network meta-analysis found atezolizumab plus bevacizumab was not superior to STRIDE for reducing the risk of death.[2](https://link.springer.com/article/10.1007/s11523-023-01026-9) A real-world target trial emulation (640 matched patients per group) found comparable overall median survival (19.4 vs 19.0 months), though one-year survival favored atezolizumab/bevacizumab (61% vs 55%) and time to first hepatic immune-related adverse event also favored that regimen.[20](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1776032/full) As second-line therapy after atezolizumab/bevacizumab, durvalumab plus tremelimumab was inferior to lenvatinib (median PFS 1.7 vs 4.2 months; median OS 5.3 vs 14.0 months), although grade 3 or higher adverse events were less frequent (21.4% vs 70.1%).[21](https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0341395) In Germany, the G-BA benefit assessment concluded that an additional benefit of tremelimumab plus durvalumab over atezolizumab plus bevacizumab in first-line advanced or unresectable HCC is not proven.[3](https://www.g-ba.de/downloads/91-1455-943/2024-10-08_Current-Version_Tremelimumab_D-924_EN.pdf) The phase 3 EMERALD-1 trial reported durvalumab with or without bevacizumab added to TACE.[22](https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2824%2902551-0/abstract)\n\n## References\n\n1. [FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma](https://pmc.ncbi.nlm.nih.gov/articles/PMC10841291/)\n2. [Tremelimumab: A Review in Advanced or Unresectable Hepatocellular Carcinoma (Targeted Oncology)](https://link.springer.com/article/10.1007/s11523-023-01026-9)\n3. [G-BA benefit assessment of tremelimumab with durvalumab in advanced/unresectable HCC](https://www.g-ba.de/downloads/91-1455-943/2024-10-08_Current-Version_Tremelimumab_D-924_EN.pdf)\n4. [Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma (HIMALAYA)](https://pubmed.ncbi.nlm.nih.gov/38319892/)\n5. [Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON)](https://clinicaltrials.gov/study/NCT03164616)\n6. [Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study](https://pubmed.ncbi.nlm.nih.gov/36327426/)\n7. [Advances in Systemic Therapy for Unresectable Hepatocellular Carcinoma: Commentary on The Impact of the STRIDE Regimen in HIMALAYA Trial](https://pmc.ncbi.nlm.nih.gov/articles/PMC12963680/)\n8. [T-Cell Receptor and Immune Gene Expression Pharmacodynamics for Durvalumab Alone and with Tremelimumab or Bevacizumab in Unresectable Hepatocellular Carcinoma (Clinical Cancer Research)](https://aacrjournals.org/clincancerres/article/32/4/694/774475/T-Cell-Receptor-and-Immune-Gene-Expression)\n9. [Tremelimumab-actl HCP Toolkit](https://aimwithimmunotherapy.org/wp-content/uploads/2026/03/Tremelimumab-actl-HCP-Toolkit_120425-FINAL-1.pdf)\n10. [abstract (thelancet.com)](https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2900544-6/abstract)\n11. [POSEIDON study protocol (NCT03164616), sponsor AstraZeneca AB](https://cdn.clinicaltrials.gov/large-docs/16/NCT03164616/Prot_002.pdf)\n12. [Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study](https://ascopubs.org/doi/10.1200/JCO.20.03555)\n13. [Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma (HIMALAYA)](https://clinicaltrials.gov/ct2/show/NCT03298451)\n14. [Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients with unresectable hepatocellular carcinoma (uHCC): HIMALAYA](https://ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.379)\n15. [Durvalumab Plus Tremelimumab: A Novel Combination Immunotherapy for Unresectable Hepatocellular Carcinoma (Liver Cancer, Karger)](https://karger.com/lic/article/11/2/87/824981/Durvalumab-Plus-Tremelimumab-A-Novel-Combination)\n16. [Tremelimumab and durvalumab ± lenvatinib plus transarterial chemoembolisation in embolisation-eligible hepatocellular carcinoma: results from the EMERALD-3 study](https://www.bjmo.be/tremelimumab-and-durvalumab-with-or-without-lenvatinib-plus-transarterial-chemoembolisation-in-embolisation-eligible-hepatocellular-carcinoma-results-from-the-emerald-3-study/)\n17. [Durvalumab With or Without Tremelimumab in Combination With Chemotherapy in First-Line Metastatic NSCLC: Five-Year Overall Survival Outcomes From the Phase 3 POSEIDON Trial](https://europepmc.org/article/MED/39243945)\n18. [IMFINZI® (durvalumab) + IMJUDO® (tremelimumab-actl) improves PFS in early liver cancer](https://business.am-news.com/am-news/article/bizwire-2026-4-2-imfinzi-durvalumab-imjudo-tremelimumab-actl-improves-pfs-in-early-liver-cancer)\n19. [Efficacy and Safety of Durvalumab plus Tremelimumab for Unresectable Hepatocellular Carcinoma: A Real-World Multicenter Observational Study](https://www.techscience.com/or/v34n9/68350)\n20. [Comparative effectiveness of two first-line, ICI-based regimens for advanced HCC: a target trial emulation using an electronic medical record network](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1776032/full)\n21. [Comparison of outcomes of second-line durvalumab plus tremelimumab versus lenvatinib following first-line atezolizumab plus bevacizumab in unresectable HCC (PLOS One)](https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0341395)\n22. [Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study](https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2824%2902551-0/abstract)\n\n---\n*Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Biologics, monoclonal antibodies, and biosimilars*\n\n*Initially written Sep 29, 2026 · Edited: Oct 15, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/durvalumab-and-tremelimumab-regimen", "markdown_url": "https://www.edgepedia.org/durvalumab-and-tremelimumab-regimen.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Durvalumab and tremelimumab regimen\", Edgepedia (EdgeChat), https://www.edgepedia.org/durvalumab-and-tremelimumab-regimen. Edgepedia Community License 1.0.", "credit_md": "\"[Durvalumab and tremelimumab regimen](https://www.edgepedia.org/durvalumab-and-tremelimumab-regimen)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/durvalumab-and-tremelimumab-regimen](https://www.edgepedia.org/durvalumab-and-tremelimumab-regimen). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Durvalumab and tremelimumab regimen\", Edgepedia (EdgeChat), https://www.edgepedia.org/durvalumab-and-tremelimumab-regimen. Edgepedia Community License 1.0.", "speakable": "The durvalumab plus tremelimumab regimen, given as the STRIDE schedule of one tremelimumab dose plus regular durvalumab, is an approved immunotherapy for unresectable liver cancer and some lung cancers." }