IMDELLTRA® SIGNIFICANTLY REDUCED RISK OF DEATH BY 40% IN SMALL CELL LUNG CANCER PATIENTS
- 40% reduction in death risk with IMDELLTRA compared to standard chemotherapy
- Significant 5.3-month improvement in median overall survival (13.6 vs 8.3 months)
- Lower rates of severe treatment-related adverse events (27% vs 62%) compared to control arm
- Fewer treatment discontinuations (3% vs 6%) than standard chemotherapy
- Improved patient-reported outcomes for cancer symptoms
- No Grade 4 or 5 cytokine release syndrome events reported
- Cytokine release syndrome occurred in 56% of patients (though mostly low grade)
- Limited progression-free survival benefit of only 0.5 months (4.2 vs 3.7 months)
Insights
Amgen's IMDELLTRA shows remarkable 40% mortality reduction in small cell lung cancer, significantly strengthening its market position in oncology therapeutics.
Amgen's Phase 3 DeLLphi-304 trial results for IMDELLTRA (tarlatamab-dlle) represent a significant breakthrough in small cell lung cancer (SCLC) treatment. The drug demonstrated a 40% reduction in death risk with median overall survival extended by more than 5 months (13.6 vs 8.3 months) compared to standard chemotherapy. This robust hazard ratio of 0.60 (p<0.001) indicates strong statistical significance.
The clinical benefits extend beyond survival metrics. IMDELLTRA showed improved progression-free survival (4.2 vs 3.7 months) and notably better patient-reported outcomes for key symptoms like dyspnea and cough. Perhaps equally important is the favorable safety profile, with lower rates of severe treatment-related adverse events (27% vs 62%) and fewer discontinuations (3% vs 6%) compared to standard chemotherapy.
For context, SCLC is notoriously difficult to treat with poor prognosis after first-line therapy. The study positions IMDELLTRA to potentially become the new standard of care in second-line SCLC treatment, a significant market opportunity. This data will likely support full FDA approval, following its previous accelerated approval.
The publication in The New England Journal of Medicine and presentation at ASCO 2025 adds scientific credibility and visibility. With validation from a leading expert at Memorial Sloan Kettering Cancer Center, IMDELLTRA is positioned to transform the treatment paradigm for SCLC, representing a substantial advancement in Amgen's oncology portfolio that could drive significant revenue growth.
Breakthrough Second-Line Treatment Demonstrated Survival Advantage over Standard-of-Care Chemotherapy
Late-Breaking Data Presented at ASCO 2025 and Simultaneously Published in The New England Journal of Medicine
"Small cell lung cancer is an extraordinarily aggressive and difficult-to-treat disease, and those living with SCLC often experience limited benefit with first line treatment," said Jay Bradner, M.D., executive vice president, Research and Development, at Amgen. "These data underscore IMDELLTRA's potential to transform patient outcomes and the small cell lung cancer treatment paradigm."
At the planned interim analysis, DeLLphi-304 met its primary OS endpoint and key secondary progression-free survival (PFS) endpoint. Additionally, IMDELLTRA significantly improved patient-reported outcomes (PRO) for cancer-related symptoms of dyspnea and cough compared to the control arm.
"The data from DeLLphi-304 mark a major milestone for people with relapsed small cell lung cancer. Tarlatamab is associated with significant improvements in both overall and progression-free survival over standard chemotherapy in patients with recurrent or progressive disease," said Charles Rudin, M.D., Ph.D., deputy director, Memorial Sloan Kettering Cancer Center. "This study also provides confirmatory data on management of potential toxicities associated with bispecific T-cell engager therapies in a large patient cohort, which is crucial to continuing to improve the experience of patients treated with these medicines."
At a median follow-up of 11.2 months for IMDELLTRA and 11.7 months for the control arm, data from the global Phase 3 DeLLphi-304 clinical trial showed a median OS of 13.6 months with IMDELLTRA compared to 8.3 months with local SOC chemotherapy (HR, 0.60;
The safety profile for IMDELLTRA in DeLLphi-304 was consistent with its known profile. In DeLLphi-304, lower rates of grade 3 or higher treatment-related adverse events (TRAEs) occurred with IMDELLTRA versus the control arm (
DeLLphi-304 is a global Phase 3, randomized, controlled, open-label clinical trial evaluating the efficacy and safety of IMDELLTRA as a treatment for patients living with SCLC who progressed on or after a single line of platinum-based chemotherapy.1 Five hundred and nine patients were randomized to receive either IMDELLTRA or local SOC chemotherapy (topotecan in all countries except
About IMDELLTRA® (tarlatamab-dlle)
IMDELLTRA is a first-in-class targeted immunotherapy engineered by Amgen researchers to bind to both DLL3 on tumor cells and CD3 on T cells, thereby activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.3,4 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85
IMDELLTRA® (tarlatamab-dlle) U.S. Indication
IMDELLTRA® (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
About Small Cell Lung Cancer (SCLC)
SCLC is one of the most aggressive and devastating solid tumor malignancies, with a 5
About Tarlatamab Clinical Trials
Amgen's robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as a monotherapy and as part of combination regimens, including in both earlier stages of SCLC and earlier lines of treatment.
Tarlatamab is being investigated in multiple studies including DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard-of-care therapies in first-line ES-SCLC; DeLLphi-304, a randomized Phase 3 study comparing tarlatamab monotherapy with standard-of-care chemotherapy in second-line treatment of SCLC; DeLLphi-305, a randomized Phase 3 study comparing tarlatamab in combination with durvalumab versus durvalumab alone as first-line maintenance treatment in ES-SCLC; DeLLphi-306, a randomized placebo-controlled Phase 3 study of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC; DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab in second line or later ES-SCLC; DeLLphi-309, a Phase 2 study evaluating alternative intravenous dosing regimens with tarlatamab in second-line ES-SCLC; DeLLphi-310, a Phase 1b study of tarlatamab in combination with YL201 with or without anti-programmed death ligand 1 (PD-L1) in patients with ES-SCLC; and DeLLphi-312, a Phase 3 study evaluating tarlatamab as an induction and maintenance therapy in first-line treatment of ES-SCLC in combination with carboplatin, etoposide, and durvalumab.11
For more information, please visit www.tarlatamabclinicaltrials.com.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, YouTube and Threads.
IMDELLTRA® (tarlatamab-dlle) Important Safety Information (USPI)
WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
- Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA®. Initiate treatment with IMDELLTRA® using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA® until CRS resolves or permanently discontinue based on severity.
- Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA®. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRA® until ICANS resolves or permanently discontinue based on severity.
WARNINGS AND PRECAUTIONS
- Cytokine Release Syndrome (CRS): IMDELLTRA® can cause CRS including serious or life-threatening reactions. In the pooled safety population, CRS occurred in
55% of patients who received IMDELLTRA®, including34% Grade 1,19% Grade 2,1.1% Grade 3 and0.5% Grade 4. Recurrent CRS occurred in24% of patients, including18% Grade 1 and6% Grade 2.
Most events (43% ) of CRS occurred after the first dose, with29% of patients experiencing any grade CRS after the second dose and9% of patients experiencing CRS following the third dose or later. Following the Day 1, Day 8, and Day 15 infusions,16% ,4.3% and2.1% of patients experienced ≥ Grade 2 CRS, respectively. The median time to onset of all grade CRS from most recent dose of IMDELLTRA® was 13.5 hours (range: 1 to 268 hours). The median time to onset of ≥ Grade 2 CRS from most recent dose of IMDELLTRA® was 14.6 hours (range: 2 to 566 hours).
Clinical signs and symptoms of CRS included pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and vomiting. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).
Administer IMDELLTRA® following the recommended step-up dosing and administer concomitant medications before and after Cycle 1 IMDELLTRA® infusions as described in Table 3 of the Prescribing Information (PI) to reduce the risk of CRS. Administer IMDELLTRA® in an appropriate health care facility equipped to monitor and manage CRS. Ensure patients are well hydrated prior to administration of IMDELLTRA®.
Closely monitor patients for signs and symptoms of CRS during treatment with IMDELLTRA®. At the first sign of CRS, immediately discontinue IMDELLTRA® infusion, evaluate the patient for hospitalization and institute supportive care based on severity. Withhold or permanently discontinue IMDELLTRA® based on severity. Counsel patients to seek medical attention should signs or symptoms of CRS occur. - Neurologic Toxicity, Including ICANS: IMDELLTRA® can cause serious or life-threatening neurologic toxicity, including ICANS. In the pooled safety population, neurologic toxicity, including ICANS, occurred in
47% of patients who received IMDELLTRA®, including10% Grade 3. The most frequent neurologic toxicities were headache (14% ), peripheral neuropathy (7% ), dizziness (7% ), insomnia (6% ), muscular weakness (3.7% ), delirium (2.1% ), syncope (1.6% ), and neurotoxicity (1.1% ).
ICANS occurred in9% of IMDELLTRA®-treated patients. Recurrent ICANS occurred in1.6% of patients. Most patients experienced ICANS following Cycle 2 Day 1 (24% ). Following Day 1, Day 8, and Day 15 infusions,0.5% ,0.5% and3.7% of patients experienced ≥ Grade 2 ICANS, respectively. The median time to onset of ICANS from the first dose of IMDELLTRATM was 29.5 days (range: 1 to 154 days). ICANS can occur several weeks following administration of IMDELLTRATM. The median time to resolution of ICANS was 33 days (range: 1 to 93 days).
The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.
Patients receiving IMDELLTRA® are at risk of neurologic adverse reactions and ICANS resulting in depressed level of consciousness. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, in the event of any neurologic symptoms until they resolve.
Closely monitor patients for signs and symptoms of neurologic toxicity and ICANS during treatment. At the first sign of ICANS, immediately evaluate the patient and provide supportive therapy based on severity. Withhold IMDELLTRA® or permanently discontinue based on severity. - Cytopenias: IMDELLTRA® can cause cytopenias including neutropenia, thrombocytopenia, and anemia. In the pooled safety population, decreased neutrophils occurred in
12% including6% Grade 3 or 4 of IMDELLTRA®-treated patients. The median time to onset for Grade 3 or 4 neutropenia was 29.5 days (range: 2 to 213). Decreased platelets occurred in33% including3.2% Grade 3 or 4. The median time to onset for Grade 3 or 4 decreased platelets was 50 days (range: 3 to 420). Decreased hemoglobin occurred in58% including5% Grade 3 or 4. Febrile neutropenia occurred in0.5% of patients treated with IMDELLTRA®.
Monitor patients for signs and symptoms of cytopenias. Perform complete blood counts prior to treatment with IMDELLTRA®, before each dose, and as clinically indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue IMDELLTRA®. - Infections: IMDELLTRA® can cause serious infections, including life-threatening and fatal infections. In the pooled safety population, infections, including opportunistic infections, occurred in
41% of patients who received IMDELLTRA®. Grade 3 or 4 infections occurred in13% of patients. The most frequent infections were COVID-19 (9% , majority during the COVID-19 pandemic), urinary tract infection (10% ), pneumonia (9% ), respiratory tract infection (3.2% ), and candida infection (3.2% ).
Monitor patients for signs and symptoms of infection prior to and during treatment with IMDELLTRA® and treat as clinically indicated. Withhold or permanently discontinue IMDELLTRA® based on severity. - Hepatotoxicity: IMDELLTRA® can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in
42% , with Grade 3 or 4 ALT elevation occurring in2.1% . Elevated AST occurred in44% of patients, with Grade 3 or 4 AST elevation occurring in3.2% . Elevated bilirubin occurred in15% of patients; Grade 3 or 4 total bilirubin elevations occurred in1.6% of patients. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with IMDELLTRA®, before each dose, and as clinically indicated. Withhold IMDELLTRA® or permanently discontinue based on severity. - Hypersensitivity: IMDELLTRA® can cause severe hypersensitivity reactions. Clinical signs and symptoms of hypersensitivity may include, but are not limited to, rash and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity during treatment with IMDELLTRA® and manage as clinically indicated. Withhold or consider permanent discontinuation of IMDELLTRA® based on severity.
- Embryo-Fetal Toxicity: Based on its mechanism of action, IMDELLTRA® may cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMDELLTRA® and for 2 months after the last dose.
ADVERSE REACTIONS
- The most common (>
20% ) adverse reactions were CRS (55% ), fatigue (51% ), pyrexia (36% ), dysgeusia (36% ), decreased appetite (34% ), musculoskeletal pain (30% ), constipation (30% ), anemia (27% ) and nausea (22% ). The most common (≥2% ) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (57% ), decreased sodium (16% ), increased uric acid (10% ), decreased total neutrophils (6% ), decreased hemoglobin (5% ), increased activated partial thromboplastin time (5% ), decreased potassium (5% ), increased aspartate aminotransferase (3.2% ), decreased white blood cells (3.8% ), decreased platelets (3.2% ), and increased alanine aminotransferase (2.1% ). - Serious adverse reactions occurred in
58% of patients. Serious adverse reactions in >3% of patients included CRS (24% ), pneumonia (6% ), pyrexia (3.7% ), and hyponatremia (3.6% ). Fatal adverse reactions occurred in2.7% of patients including pneumonia (0.5% ), aspiration (0.5% ), pulmonary embolism (0.5% ), respiratory acidosis (0.5% ), and respiratory failure (0.5% ).
DOSAGE AND ADMINISTRATION: Important Dosing Information
- Administer IMDELLTRA® as an intravenous infusion over one hour.
- Administer IMDELLTRA® according to the step-up dosing schedule in the IMDELLTRA® PI (Table 1) to reduce the incidence and severity of CRS.
- For Cycle 1, administer recommended concomitant medications before and after Cycle 1 IMDELLTRA® infusions to reduce the risk of CRS reactions as described in the PI (Table 3).
- IMDELLTRA® should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including ICANS.
- Due to the risk of CRS and neurologic toxicity, including ICANS, monitor patients from the start of the IMDELLTRA® infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting.
- Recommend that patients remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with IMDELLTRA® following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver.
- Prior to administration of IMDELLTRA® evaluate complete blood count, liver enzymes, and bilirubin before each dose, and as clinically indicated.
- Ensure patients are well hydrated prior to administration of IMDELLTRA®.
Please see IMDELLTRA® full Prescribing Information, including BOXED WARNINGS.
Amgen Forward-Looking Statements
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