Imfinzi (Durvalumab)
durvalumab — human IgG1 kappa anti-PD-L1 monoclonal antibody
Indications
Durvalumab holds one of the broadest indication portfolios among PD-L1 inhibitors, spanning lung, biliary, liver, endometrial, bladder, and gastric cancers. First approved in May 2017 for urothelial carcinoma (subsequently withdrawn), the label has expanded rapidly with multiple perioperative indications approved between December 2024 and November 2025. The table below reflects all currently FDA-approved indications.
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Resectable NSCLC — neoadjuvant / adjuvant | Adults (≥4 cm and/or node+, no EGFR/ALK) | + platinum chemo (neoadj) → mono (adj) | FDA Approved |
| Unresectable Stage III NSCLC | Adults (no progression after cCRT) | Monotherapy (consolidation) | FDA Approved |
| Metastatic NSCLC | Adults (no EGFR/ALK) | + tremelimumab + platinum chemo | FDA Approved |
| LS-SCLC (consolidation) | Adults (no progression after cCRT) | Monotherapy | FDA Approved |
| ES-SCLC — first-line | Adults | + etoposide + carbo or cisplatin | FDA Approved |
| Biliary tract cancer (BTC) | Adults (locally advanced or metastatic) | + gemcitabine + cisplatin | FDA Approved |
| Unresectable HCC | Adults | + tremelimumab (single dose STRIDE regimen) | FDA Approved |
| dMMR endometrial cancer | Adults (primary advanced or recurrent, dMMR by FDA-approved test) | + carboplatin + paclitaxel → mono | FDA Approved |
| Muscle-invasive bladder cancer (MIBC) | Adults | + gem + cisplatin (neoadj) → mono (adj post-cystectomy) | FDA Approved |
| Gastric / GEJ adenocarcinoma (resectable) | Adults | + FLOT (neoadj/adj) → mono | FDA Approved |
Durvalumab is distinguished by its consolidation role following chemoradiation in both unresectable Stage III NSCLC (PACIFIC trial, approved February 2018) and LS-SCLC (ADRIATIC trial, approved December 2024), settings where no other PD-1/PD-L1 inhibitor is approved. The November 2025 gastric/GEJ approval (MATTERHORN trial) made it the first and only perioperative immunotherapy for this cancer type. The previously held urothelial carcinoma indication (accelerated approval May 2017) was voluntarily withdrawn in February 2021.
Urothelial carcinoma (locally advanced/metastatic): The original accelerated approval for post-platinum UC was voluntarily withdrawn on February 22, 2021 after the confirmatory phase 3 DANUBE trial did not meet its primary endpoints. The separate MIBC perioperative indication (approved March 2025, based on NIAGARA) is a distinct approval. Evidence quality: low.
Dosing
Durvalumab dosing varies considerably by indication, with most regimens using a 1,500 mg flat dose for patients ≥30 kg. Weight-based dosing (10–20 mg/kg) is used for patients weighing less than 30 kg. No dose reductions are recommended. All infusions are administered over 60 minutes. When given with tremelimumab, the tremelimumab infusion is given first.
Monotherapy Indications
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Unresectable Stage III NSCLC (post-cCRT consolidation) | 10 mg/kg Q2W or 1,500 mg Q4W | Same | 1,500 mg Q4W | Maximum 12 months. Start within 1–42 days after cCRT completion. <30 kg: 10 mg/kg Q2W only |
| LS-SCLC (post-cCRT consolidation) | 1,500 mg Q4W | Same | 1,500 mg Q4W | Maximum 24 months or until progression. <30 kg: 20 mg/kg Q4W |
Perioperative / Neoadjuvant-Adjuvant Regimens
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Resectable NSCLC (neoadj + adj) | 1,500 mg Q3W + platinum chemo (neoadj, up to 4 cycles) | 1,500 mg Q4W mono (adj, up to 12 cycles) | 1,500 mg Q4W | No EGFR/ALK. Tumours ≥4 cm and/or node-positive. <30 kg: 20 mg/kg neoadj Q3W, 20 mg/kg adj Q4W |
| MIBC (neoadj + adj post-cystectomy) | 1,500 mg Q3W + gem + cisplatin (neoadj, 4 cycles) | 1,500 mg Q4W mono (adj, up to 8 cycles) | 1,500 mg Q4W | Neoadjuvant followed by radical cystectomy then adjuvant durvalumab. <30 kg: 20 mg/kg Q3W neoadj, 20 mg/kg Q4W adj |
| Gastric / GEJ adenocarcinoma (perioperative) | 1,500 mg Q4W + FLOT (up to 4 cycles: 2 neoadj + 2 adj) | 1,500 mg Q4W mono (up to 10 cycles) | 1,500 mg Q4W | FLOT = fluorouracil + leucovorin + oxaliplatin + docetaxel. 2 cycles pre-surgery + 2 cycles post-surgery with FLOT, then up to 10 cycles mono. Max 12 cycles after surgery. <30 kg: 20 mg/kg Q4W |
Combination Regimens (Non-Perioperative)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| ES-SCLC 1L + etoposide + carbo/cisplatin | 1,500 mg Q3W + chemo (4 cycles) | 1,500 mg Q4W mono | 1,500 mg Q4W | Either carboplatin or cisplatin permitted. Continue maintenance until progression. <30 kg: 20 mg/kg Q3W → 10 mg/kg Q2W |
| BTC + gemcitabine + cisplatin | 1,500 mg Q3W + chemo (up to 8 cycles) | 1,500 mg Q4W mono | 1,500 mg Q4W | Continue maintenance until progression or toxicity. <30 kg: 20 mg/kg Q3W → 20 mg/kg Q4W |
| uHCC + tremelimumab (STRIDE regimen) | 1,500 mg + tremelimumab 300 mg (single dose, day 1 cycle 1) | 1,500 mg Q4W mono | 1,500 mg Q4W | Only ONE dose of tremelimumab 300 mg, then durvalumab mono. Continue until progression. <30 kg: 20 mg/kg + treme 4 mg/kg |
| Metastatic NSCLC + tremelimumab + platinum chemo | 1,500 mg Q3W + treme 75 mg + chemo (4 cycles) | 1,500 mg Q4W + 5th treme 75 mg at week 16 | 1,500 mg Q4W | Complex schedule: treme for up to 5 doses total (4 during chemo + 1 at week 16). Optional pemetrexed maintenance for non-squamous. |
| dMMR endometrial cancer + carbo + paclitaxel | 1,120 mg Q3W + carbo + pac (6 cycles) | 1,500 mg Q4W mono | 1,500 mg Q4W | Note unique 1,120 mg induction dose (not 1,500 mg). dMMR status by FDA-approved test. <30 kg: 15 mg/kg Q3W → 20 mg/kg Q4W |
Durvalumab has several dosing nuances that distinguish it from other checkpoint inhibitors. The dMMR endometrial cancer induction dose is uniquely 1,120 mg (not 1,500 mg), reflecting the dose used in the DUO-E trial. The HCC STRIDE regimen uses only a single priming dose of tremelimumab 300 mg followed by durvalumab monotherapy maintenance, which differs fundamentally from the multi-dose ipilimumab combinations used with nivolumab. The LS-SCLC consolidation indication allows treatment for up to 24 months, the longest approved duration for any single-agent checkpoint inhibitor consolidation.
Pharmacology
Mechanism of Action
Durvalumab is a fully human IgG1 kappa monoclonal antibody that selectively binds PD-L1 with high affinity, blocking its interactions with both PD-1 and CD80 (B7.1). This dual blockade distinguishes PD-L1-targeting agents from PD-1 inhibitors, which block PD-L1 and PD-L2 binding to PD-1 but do not affect the PD-L1/B7.1 axis. By preventing PD-L1-mediated suppression of T-cell activity, durvalumab restores anti-tumour immune surveillance.
The Fc domain of durvalumab is engineered with a triple mutation in the constant region that eliminates antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). This modification is critical because PD-L1 is also expressed on activated T cells; an unmodified IgG1 could paradoxically deplete the very immune effector cells it aims to activate.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | IV route: 100% bioavailability. Greater-than-proportional exposure at <3 mg/kg; dose-proportional at ≥3 mg/kg. | Fixed dosing (1,500 mg) is preferred over weight-based dosing for most indications. PK is similar between single-agent and combination settings. |
| Distribution | Vdss = 5.6 L. Limited extravascular distribution consistent with IgG1 properties. | Small Vd reflects primarily intravascular and interstitial distribution. No clinically relevant effects of body weight, age, sex, or albumin. |
| Metabolism | Catabolised by non-specific protein catabolism and the reticuloendothelial system. No CYP involvement. FcRn recycling extends circulating half-life. | No hepatic CYP drug interactions expected. Clearance not meaningfully affected by mild renal or hepatic impairment. |
| Elimination | Baseline CL geometric mean: ~8.2 mL/h. CL decreases ~23% over 1 year (time-varying). Terminal t½: 18–21 days. Steady state: ~16 weeks. | Longer time to steady state than some other checkpoint inhibitors. Time-varying CL likely reflects tumour burden reduction. ADA incidence ~3.2% with no clinically significant PK or safety impact. |
Side Effects
Durvalumab’s toxicity profile follows the class-wide pattern of immune-mediated adverse reactions, with notable differences by clinical setting. The pneumonitis rate is substantially higher in patients who have received recent thoracic radiation (PACIFIC, ADRIATIC). The addition of tremelimumab increases the frequency and severity of colitis, hepatitis, and pancreatitis. Data are from the FDA PI pooled analyses and pivotal trials.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Fatigue / asthenia | 20–49% | Universal across settings. Higher with chemotherapy combinations. Exclude endocrine causes. |
| Pneumonitis / radiation pneumonitis | 2.4–18.3% | 2.4% without prior radiation; 18.3% post-cCRT (PACIFIC); 14% post-cCRT (ADRIATIC LS-SCLC). Key toxicity in consolidation settings. |
| Nausea | 20–38% | Higher with platinum-based chemotherapy. Usually Grade 1–2. |
| Rash | 20–36% | Higher with tremelimumab combinations. Includes maculopapular, dermatitis. |
| Cough / dyspnoea | 20–35% | Common in all lung cancer settings. Distinguish from pneumonitis and progression. |
| Decreased appetite | 20–25% | Monitor weight; exclude adrenal insufficiency. |
| Alopecia | 20–35% | With chemotherapy combinations (ES-SCLC, NSCLC, endometrial); not with monotherapy. |
| Constipation | 20–28% | With chemotherapy combinations. Manageable with standard interventions. |
| Diarrhoea | 12–27% | Higher with tremelimumab (up to 27% in uHCC). Distinguish from immune-mediated colitis. |
| Hypothyroidism | 8.3–14% | 8.3% monotherapy (n=1889); 8.6% with treme + chemo; 11% with treme alone; 14% with carbo/pac (endometrial). Mostly permanent; requires levothyroxine. |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Immune-mediated hepatitis | 2.8–7.5% | 2.8% monotherapy; 3.9% with treme + chemo; 7.5% with tremelimumab alone. Fatal events reported (0.2–0.8%). |
| Immune-mediated colitis | 2–6.5% | 2% monotherapy; 6% with treme; 6.5% with treme + chemo. Intestinal perforation reported with tremelimumab combos. |
| Hyperthyroidism | 2.1–5% | 2.1% monotherapy; 4.6% with treme; 5% with treme + chemo. Often transient, preceding hypothyroidism. |
| Infusion-related reactions | 2.2% | Grade 3 in 0.3%. Consider premedication if Grade 1–2 reaction occurs. |
| Immune-mediated rash / dermatitis | 1.8–7.2% | 1.8% monotherapy; 4.9% with treme; 7.2% with treme + chemo. |
| Adrenal insufficiency | 0.5–2.2% | 0.5% monotherapy; 1.5% with treme; 2.2% with treme + chemo. May require lifelong replacement. |
| Immune-mediated nephritis | 0.5–1% | 0.5% monotherapy; 1% with treme. Monitor creatinine each cycle. |
| Immune-mediated pancreatitis | 0–2.3% | Not seen with monotherapy; 2.3% with tremelimumab combinations. Unique to CTLA-4 co-blockade. |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Immune-mediated pneumonitis | 2.4% (mono, no XRT); 14–18% (post-cCRT) | 1–12 months | Withhold for Grade 2; permanently discontinue for Grade 3–4. Corticosteroids 1–2 mg/kg/day. Fatal events reported (<0.1–1.1%). |
| Immune-mediated hepatitis | 2.8% (mono); fatal 0.2% | 1–6 months | Withhold for ALT/AST >3–8× ULN; permanently discontinue for >8× ULN. High-dose corticosteroids; mycophenolate if refractory. |
| Immune-mediated colitis / intestinal perforation | 2% (mono); 6–6.5% (+ treme) | 1–10 months | Withhold for Grade 2; permanently discontinue for Grade 3 (with treme) or Grade 4. Infliximab for steroid-refractory. Intestinal perforation: permanently discontinue regardless of grade. |
| Immune-mediated myocarditis | Rare (<1%); potentially fatal | First 1–3 cycles | Permanently discontinue for Grade 2–4. Immediate high-dose corticosteroids. Cardiology consultation. |
| Type 1 diabetes mellitus | <0.1–0.5% | Variable | Initiate insulin. Monitor blood glucose. Long-term insulin required. DKA possible at presentation. |
| Severe dermatologic reactions (SJS, TEN, DRESS) | Rare (<1%) | Days to weeks | Withhold for suspected; permanently discontinue if confirmed. |
| Neurological toxicity (encephalitis, Guillain-Barré, myasthenia gravis) | Rare (<1%) | Variable | Withhold for Grade 2; permanently discontinue for Grade 3–4. Corticosteroids; IVIG as indicated. |
Pneumonitis is the defining toxicity concern for durvalumab, particularly in the PACIFIC (18.3%) and ADRIATIC (14%) consolidation settings following chemoradiation. Distinguishing immune-mediated pneumonitis from radiation pneumonitis can be challenging; both may coexist. Any new or worsening respiratory symptoms should prompt CT imaging and potential bronchoscopy. Corticosteroids (1–2 mg/kg/day prednisone) should be initiated promptly for Grade 2 or higher pneumonitis, with a slow taper over at least 4 weeks.
Drug Interactions
No formal pharmacokinetic drug-drug interaction studies have been conducted with durvalumab. As a monoclonal antibody cleared by protein catabolism, it does not interact with CYP enzymes. All clinically relevant interactions are pharmacodynamic.
Monitoring
- Liver Function (AST, ALT, bilirubin)Baseline and before each dose
RoutinePI specifies evaluation at baseline and periodically. Higher threshold for patients with hepatic tumour involvement. Heightened vigilance with tremelimumab combinations (hepatitis up to 7.5%). - Renal Function (creatinine)Baseline and before each dose
RoutineNephritis occurs in 0.5–1%. Withhold for Grade 2–3 creatinine elevation; permanently discontinue for Grade 4. - Thyroid Function (TSH, free T4)Baseline and before each dose
RoutineHypothyroidism: 8–14%; hyperthyroidism: 2–5%. PI specifies thyroid function at baseline and periodically. Most hypothyroidism requires permanent replacement. - ACTH / CortisolBaseline and before each dose
RoutineUniquely, the PI specifies ACTH monitoring at baseline and before each dose, reflecting the clinical importance of adrenal insufficiency detection. - Pulmonary AssessmentIf respiratory symptoms develop; baseline CT in post-CRT patients
Trigger-basedPneumonitis rates up to 18.3% in post-radiation settings. Any new cough, dyspnoea, or hypoxia warrants urgent CT chest. Distinguish from radiation recall. - Blood GlucosePeriodically
Trigger-basedType 1 DM is rare but may present as DKA. Monitor for new hyperglycaemia symptoms. - Amylase / LipaseIf abdominal symptoms develop, especially with tremelimumab
Trigger-basedImmune-mediated pancreatitis (2.3% with tremelimumab) is unique to CTLA-4-containing regimens. Not seen with monotherapy. - CBCBefore each cycle with chemotherapy
RoutineEssential during chemotherapy combinations. Immune-mediated cytopenias are rare but reported.
Contraindications & Cautions
Absolute Contraindications
The FDA PI lists no absolute contraindications for durvalumab.
Relative Contraindications (Specialist Input Recommended)
- Active, severe autoimmune disease requiring systemic immunosuppression: risk of life-threatening flare.
- Prior organ transplantation: high risk of allograft rejection. PI includes specific warning (Section 5.3).
- Prior life-threatening irAE from any PD-1/PD-L1 or CTLA-4 inhibitor: rechallenge carries substantial risk.
- Pregnancy or planned pregnancy: durvalumab can cause fetal harm. Contraception required during treatment and for 3 months after last dose.
Use with Caution
- Controlled autoimmune conditions: elevated flare risk; close monitoring required.
- Pre-existing interstitial lung disease or recent thoracic radiation: substantially higher pneumonitis risk (up to 18%).
- Moderate-to-severe hepatic impairment: not studied; use with caution.
Durvalumab can cause severe and fatal immune-mediated adverse reactions in any organ system, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, pancreatitis, myocarditis, and neurological toxicities. These may occur during or after treatment. Complications of allogeneic HSCT (including fatal GVHD, VOD, and steroid-requiring febrile syndrome) can occur in patients who receive PD-1/PD-L1 inhibitors before or after transplant.
Patient Counselling
Purpose of Therapy
Durvalumab is an immunotherapy that helps the immune system fight cancer by blocking a protein called PD-L1 that tumour cells use to evade detection. Depending on the cancer type, it may be given before surgery, after surgery, after chemoradiation, or as ongoing treatment with chemotherapy.
How to Take
Durvalumab is given by intravenous infusion over 60 minutes at the treatment centre. The schedule varies by indication but is typically every 3 or 4 weeks. When given with tremelimumab, that infusion is administered first, followed by durvalumab.
Sources
- AstraZeneca. IMFINZI (durvalumab) injection, for intravenous use. Full Prescribing Information. Revised 03/2025, supplemental 11/2025. FDA.govPrimary source for all dosing, indications, adverse reactions, and warnings in this monograph.
- Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018;379(24):2342–2350. doi:10.1056/NEJMoa1809697PACIFIC: landmark trial establishing durvalumab consolidation as standard of care in unresectable Stage III NSCLC.
- Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line ES-SCLC (CASPIAN). Lancet. 2019;394(10212):1929–1939. doi:10.1016/S0140-6736(19)32222-6CASPIAN: basis for durvalumab + chemo in first-line ES-SCLC.
- Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1). NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2200015TOPAZ-1: established durvalumab + gemcitabine/cisplatin as first-line standard in advanced BTC.
- Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (HIMALAYA). NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2100070HIMALAYA: basis for the STRIDE regimen (single tremelimumab priming dose + durvalumab) in unresectable HCC.
- Heymach JV, Harpole D, Mok T, et al. Perioperative durvalumab for resectable non-small-cell lung cancer (AEGEAN). N Engl J Med. 2023;389(18):1672–1684. doi:10.1056/NEJMoa2304875AEGEAN: basis for perioperative durvalumab + chemo in resectable NSCLC.
- Cheng Y, Spigel DR, Cho BC, et al. Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer (ADRIATIC). N Engl J Med. 2024;391(14):1313–1327. doi:10.1056/NEJMoa2404873ADRIATIC: basis for durvalumab consolidation in LS-SCLC, first checkpoint inhibitor approved in this setting.
- Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer (NIAGARA). N Engl J Med. 2024;391(19):1773–1786. doi:10.1056/NEJMoa2408154NIAGARA: basis for perioperative durvalumab in muscle-invasive bladder cancer.
- Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer (MATTERHORN). N Engl J Med. 2025;393(3):217–230. doi:10.1056/NEJMoa2503701MATTERHORN: first perioperative immunotherapy approved for resectable gastric/GEJ adenocarcinoma.
- NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. Version 4.2026. NCCN.orgIncorporates durvalumab as preferred in Stage III NSCLC consolidation and perioperative resectable NSCLC.
- Brahmer JR, Abu-Sbeih H, Ascierto PA, et al. SITC clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021;9(6):e002435. doi:10.1136/jitc-2021-002435Comprehensive irAE management guidelines applicable across PD-1/PD-L1 and CTLA-4 inhibitor classes.
- Baverel PG, Dubois VFS, Jin CY, et al. Population pharmacokinetics of durvalumab in cancer patients and association with longitudinal biomarkers of disease status. Clin Pharmacol Ther. 2018;103(4):631–642. doi:10.1002/cpt.982Definitive population PK model establishing two-compartment PK, time-varying clearance, and covariate effects on durvalumab exposure.