IMFINZI ® (durvalumab) plus tarlatamab-dlle reduced the risk of death by 58% in 1st-line extensive-stage small cell lung cancer in the DeLLphi-305 Phase III trial
WILMINGTON, Del.--( BUSINESS WIRE)--Landmark results from the DeLLphi-305 Phase III trial showed IMFINZI ® (durvalumab) plus Amgen’s tarlatamab-dlle demonstrated a statistically significant and highly clinically meaningful improvement in the primary endpoint of overall survival (OS) and in the key secondary endpoint of progression-free survival (PFS) versus IMFINZI alone as a 1st-line maintenance treatment. The trial included patients with extensive-stage small cell lung cancer (ES-SCLC) who had not progressed following standard induction treatment with IMFINZI plus platinum chemotherapy (investigator’s choice of carboplatin or cisplatin) and etoposide.
These results will be presented today in a Proffered Paper session during Presidential Symposium I at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain (abstract #LBA3). 1 They were also simultaneously published in The New England Journal of Medicine.
In a planned interim analysis, IMFINZI plus tarlatamab-dlle reduced the risk of death by 58% compared to IMFINZI alone (based on an OS hazard ratio [HR] of 0.42; 95% confidence interval [CI] 0.32-0.54; p<0.001) at a median follow-up of approximately 16 months. Median OS was 21.1 months for the combination versus 12.7 months for IMFINZI alone. An estimated 79% of patients treated with the combination were alive at one year compared to 53% for IMFINZI alone.
Results from the key secondary endpoint of PFS showed the combination reduced the risk of disease progression or death by 66% compared to IMFINZI alone (based on a PFS HR of 0.34; 95% CI 0.28-0.42; p<0.001) at a median follow-up of 13.9 months. Median PFS was 7.4 months for the combination versus 1.9 months for IMFINZI alone. An estimated 38% of patients treated with the combination were alive and had not experienced disease progression at one year compared to 10% for IMFINZI alone.
The OS and PFS benefits observed were consistent across all prespecified subgroups, including patients with brain or liver metastases.
Confirmed objective response rate (ORR) with the combination was six times higher compared to IMFINZI alone (26.4% versus 4.1%; p<0.001). Median duration of response (DOR) for the combination exceeded 1 year (12.7 months) versus 5.6 months for IMFINZI alone.
Jacob Sands, MD, Associate Chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and international coordinating investigator for the trial, said: “For a disease where durable survival has remained extremely difficult to achieve, the magnitude and consistency of benefit in DeLLphi-305 are striking. Importantly, the benefit was seen across clinically relevant groups, including patients with brain metastases. Today’s remarkable results demonstrate substantial progress in our work to achieve meaningfully longer disease control and survival for patients with extensive-stage small cell lung cancer, further highlighting the importance of effective treatment at the earliest possible opportunity.”
Leora Horn, Senior Vice President, Late Development Oncology, Oncology R&D, AstraZeneca, said: “IMFINZI-based induction therapy followed by maintenance treatment with IMFINZI plus tarlatamab-dlle will redefine treatment standards for patients with extensive-stage small cell lung cancer. As the only immunotherapy to demonstrate a significant survival benefit across stages of small cell lung cancer, and now the first in combination with a T-cell engager, these important data further reinforce IMFINZI as the backbone immunotherapy in this setting.”
Summary of results: DeLLphi-305 i
IMFINZI plus tarlatamab-dlle
(n=282)
IMFINZI
(n=281)
OS
Median OS (95% CI) (in months)
21.1
(20.8-NE ii)
12.7
(11.2-14.8)
HR (95% CI)
0.42
(0.32-0.54)
Stratified log-rank, 2-sided p-value
p<0.001
OS rate at 12 months (%)
79
53
Median follow-up (in months)
15.9
16.1
PFS
Median PFS (95% CI) (in months)
7.4
(5.6-9.1)
1.9
(1.9-2.0)
HR (95% CI)
0.34
(0.28-0.42)
Stratified log-rank, 2-sided p-value
p<0.001
PFS rate at 12 months (%)
38
10
Median follow-up (in months)
13.9
13.9
IMFINZI plus tarlatamab-dlle
(n=235)
IMFINZI
(n=244)
BOR iii % (n)
Confirmed complete response iv
0.9 (2)
0.4 (1)
Confirmed partial response iv
25.5 (60)
3.7 (9)
Stable disease
54.0 (127)
30.3 (74)
Progressive disease
18.3 (43)
61.5 (150)
ORR
Confirmed ORR (%) (95% CI)
26.4
(20.9-32.5)
4.1
(2.0-7.4)
2-sided p-value
p<0.001
Median DOR in months (95% CI)
12.7
(7.4-NE)
5.6
(3.5-NE)
DOR rate at 12 months (%)
52
0
Remaining on treatment as of data cut-off i (%)
43.6
11.4
Median follow-up (in months)
10.2
8.3
IMFINZI plus tarlatamab-dlle
(n=282)
IMFINZI
(n=278)
Median duration of treatment, weeks (IQR v)
46.9 (16.4-65.6)
8.1 (4.1-20.1)
The safety and tolerability of IMFINZI plus tarlatamab-dlle was consistent with the known safety profiles of the individual medicines. Grade 3 and 4 treatment-related adverse events related to any treatment occurred in 20.9% of patients treated with the combination and 10.8% of patients treated with IMFINZI alone. Treatment with the combination resulted in a low frequency of treatment discontinuations and no treatment-related fatalities.
IMPORTANT SAFETY INFORMATION
There are no contraindications for IMFINZI ® (durvalumab) or IMJUDO ® (tremelimumab-actl).
Severe and Fatal Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.
Immune-Mediated Colitis
IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal. IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.
Immune-Mediated Hepatitis
IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal.
Immune-Mediated Endocrinopathies
Immune-Mediated Nephritis with Renal Dysfunction
IMFINZI and IMJUDO can cause immune-mediated nephritis.
Immune-Mediated Dermatology Reactions
IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.
Immune-Mediated Pancreatitis
IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.
Other Immune-Mediated Adverse Reactions
The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI and IMJUDO or were reported with the use of other immune-checkpoint inhibitors.
Infusion-Related Reactions
IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.
Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO.
Lactation
There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose.
Adverse Reactions
Unresectable Stage III NSCLC
Resectable NSCLC
Metastatic NSCLC
Limited-stage Small Cell Lung Cancer
Extensive-stage Small Cell Lung Cancer
Locally Advanced or Metastatic Biliary Tract Cancers (BTCs)
Unresectable Hepatocellular Carcinoma (HCC)
Primary Advanced or Recurrent dMMR Endometrial Cancer
BCG-Naive, High-Risk Non-Muscle-Invasive Bladder Cancer (HR-NMIBC)
Muscle-Invasive Bladder Cancer (MIBC)
Resectable Gastric Cancer/Gastroesophageal Junction Adenocarcinoma (GC/GEJC)
The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients.
Indications:
IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.
IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).
IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-authorized test.
IMFINZI in combination with Bacillus Calmette-Guérin (BCG) is indicated for the treatment of adult patients with BCG-naive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC).
IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).
IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).
Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO.
Notes
Small cell lung cancer
Lung cancer is the leading cause of cancer death globally, accounting for almost one in five (19%) cancer deaths. 2,3 Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% classified as SCLC. 4
About two-thirds of SCLC patients are diagnosed with ES-SCLC, a highly aggressive, fast-growing form of lung cancer characterized by rapid tumor progression and metastatic spread to organs such as the brain and liver. 5 In 2026, an estimated 195,000 people globally will be treated for ES-SCLC. 6
Immune checkpoint inhibitors such as IMFINZI have led to significant improvements in OS in ES-SCLC, establishing a 1st-line standard of care. However, many patients still experience disease progression due to the aggressive nature of the disease, and median OS with the current standard of care is approximately one year. 5 Only 18.1% of limited-stage SCLC patients and 3.6% of ES-SCLC patients are alive five years after diagnosis. 7
DeLLphi-305
The DeLLphi-305 trial is sponsored by Amgen, with partial funding and IMFINZI provided by AstraZeneca. It is a global Phase III, randomized, open-label clinical trial evaluating the efficacy and safety of IMFINZI in combination with tarlatamab-dlle compared to IMFINZI alone as 1st-line maintenance treatment for patients with ES-SCLC who have not progressed following induction treatment with IMFINZI in combination with platinum chemotherapy and etoposide.
Tarlatamab-dlle is a first-in-class targeted immunotherapy that binds to both DLL3 on tumor cells and CD3 on T cells, thereby activating T cells to kill DLL3-expressing SCLC cells. DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells.
In the trial, 563 patients who completed IMFINZI -based induction treatment were randomized 1:1 to receive either IMFINZI in combination with tarlatamab-dlle or IMFINZI alone until progression or unacceptable toxicity. Following tarlatamab-dlle infusion on Cycle 1 Day 1 and Cycle 1 Day 8, patients were monitored in a healthcare setting for 1 to 2 hours (6 to 8 hours in certain regions including Europe). The trial included patients with both treated and untreated asymptomatic brain metastases at baseline.
The primary endpoint is OS for IMFINZI plus tarlatamab-dlle versus IMFINZI alone. PFS is a key secondary endpoint.
IMFINZI
IMFINZI® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.
IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of IMJUDO (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage SCLC and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of ES-SCLC.
IMFINZI is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with IMJUDO in unresectable hepatocellular carcinoma (HCC). It is also approved as a monotherapy in unresectable HCC in Japan, China and the EU, and in resectable, early-stage and locally advanced gastric and gastroesophageal junction cancers in the US, EU and Japan. Additionally, in April 2026, IMFINZI in combination with IMJUDO, lenvatinib and transarterial chemoembolization (TACE) demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of PFS versus TACE alone for patients with unresectable HCC eligible for embolization in the EMERALD-3 Phase III trial.
In bladder cancer, perioperative IMFINZI in combination with neoadjuvant chemotherapy is approved for cisplatin-eligible muscle-invasive bladder cancer (MIBC)IMFINZI in combination with Bacillus Calmette-Guérin (BCG) induction and maintenance therapy is approved in the US and other countries for patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer. In May 2026, positive high-level results from the VOLGA Phase III trial showed that perioperative treatment with IMFINZI in combination with neoadjuvant enfortumab vedotin (EV) demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and OS in patients with MIBC who were ineligible for or had refused cisplatin-based chemotherapy. In addition, perioperative IMFINZI plus IMJUDO in combination with neoadjuvant EV demonstrated a statistically significant and clinically meaningful improvement in EFS and a favorable trend for OS; however, the OS data were not statistically significant at this planned interim analysis and will be formally reassessed at a subsequent analysis. In July 2026, positive high-level results from the NILE Phase III trial showed IMFINZI plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS versus chemotherapy as 1st-line treatment for patients with PD-L1 high unresectable, locally advanced or metastatic urothelial cancer.
IMFINZI in combination with chemotherapy followed by IMFINZI monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US, EU and China). IMFINZI in combination with chemotherapy followed by olaparib and IMFINZI is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in the EU and Japan.
Since the first approval in May 2017, more than 470,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several gastrointestinal cancers.
AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.
The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including osimertinib and gefitinib; IMFINZI and IMJUDO; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan-dlnk in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.
AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.
AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors.
AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with IMJUDO as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca.
References