Tarlatamab for Small Cell Lung Cancer

(DeLLphi-306 Trial)

Recruiting at 314 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: Corticosteroids, Immunosuppressants, DLL3 inhibitors

Disqualifiers: Extensive-stage SCLC, Recent myocardial infarction, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 28 days per cycle

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tarlatamab (also known as Imdelltra, tarlatamab-dlle, AMG757, or AMG-757) to determine if it can help people with small cell lung cancer live longer without disease progression. Participants will receive either tarlatamab or a placebo (a harmless, inactive substance) to compare results. Suitable participants should have previously undergone chemotherapy and radiation for small cell lung cancer and show no disease progression. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on another anti-cancer therapy or systemic corticosteroid therapy within 7 days before joining the study.

Is there any evidence suggesting that tarlatamab is likely to be safe for humans?

Research shows that tarlatamab, the treatment being tested, is generally safe but has some side effects. In studies with patients who had already received extensive treatment for small cell lung cancer, tarlatamab effectively fought tumors. However, some patients experienced side effects like cytokine release syndrome (CRS), where the body reacts strongly to the treatment, and ICANS, which can affect the nervous system.

These side effects appeared in real-world cases where patients received tarlatamab as part of their regular treatment. While these effects can be serious, healthcare professionals can manage them. Overall, tarlatamab has been used safely in many patients and has shown promise in improving survival rates. It is important to discuss any concerns with the medical team and understand what to expect when considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for small cell lung cancer?

Unlike the standard treatments for small cell lung cancer, which often involve chemotherapy and radiation, Tarlatamab represents a new approach by engaging the immune system to target cancer cells. Tarlatamab is a bispecific T-cell engager (BiTE), which means it is designed to link T-cells, a type of immune cell, directly to cancer cells, potentially leading to more precise and potent destruction of the tumor. Researchers are excited about Tarlatamab because it offers a novel mechanism that could enhance the effectiveness of the immune response against cancer, possibly leading to improved outcomes for patients with small cell lung cancer.

What evidence suggests that tarlatamab could be an effective treatment for small cell lung cancer?

Research has shown that tarlatamab, which participants in this trial may receive, may help treat small cell lung cancer. In one study, patients who took tarlatamab every two weeks saw their tumors shrink significantly and lived longer. Another study found that tarlatamab lowered the risk of death by 40% and increased survival by more than five months compared to older treatments. Tarlatamab targets a protein called DLL3 on cancer cells, enabling the immune system to attack the cancer. These findings suggest that tarlatamab could be a promising option for patients with this type of lung cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Adults diagnosed with limited-stage small-cell lung cancer (LS-SCLC) who have completed chemoradiotherapy without disease progression. Participants must be in good physical condition, not pregnant or planning to become pregnant, and willing to use contraception. Excluded are those with extensive-stage SCLC, recent heart issues, other cancers within 2 years (with exceptions), active infections, HIV/hepatitis, prior immune therapy complications, or organ transplants.

Inclusion Criteria

Participant has provided informed consent prior to initiation of any study specific activities/procedures.

I am at least 18 years old or the legal age in my country.

My lung cancer is confirmed to be small-cell type.

Exclusion Criteria

Other Exclusions

Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the participant and investigator's knowledge.

My condition is related to my disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tarlatamab or placebo on Cycle 1 Day 1, 8, and 15, and once every 2 weeks thereafter

28 days per cycle

3 visits in the first cycle, then bi-weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tarlatamab

Trial Overview The trial is testing the effectiveness of Tarlatamab compared to a placebo in preventing cancer progression after initial treatment for LS-SCLC. Patients will either receive Tarlatamab or a placebo and will be monitored for changes in their cancer status over time.

How Is the Trial Designed?

Group I: Tarlatamab Experimental Treatment 1 Intervention

Participants will receive tarlatamab on Cycle 1 Day 1, 8 and 15, and once every 2 weeks (Q2W) thereafter (cycle is 28 days).

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo on Cycle 1 Day 1, 8 and 15, and Q2W thereafter (cycle is 28 days).

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

DLL3 is a promising target for treating small cell lung cancer (SCLC) due to its overexpression on cancer cells and minimal presence on normal cells, making it a potential avenue for targeted therapies.

While the DLL3-targeting antibody-drug conjugate Rova-T was halted in phase 3 trials due to lack of efficacy, ongoing development of other DLL3-targeting therapies, such as T-cell engagers and CAR T-cell therapies, shows potential for improving treatment outcomes in SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer. Rudin, CM., Reck, M., Johnson, ML., et al.[2023]

Tarlatamab is a promising investigational treatment for small cell lung cancer, specifically targeting the delta-like ligand 3 protein, and has shown effectiveness in patients whose cancer progressed after previous therapies.

Despite its potential benefits, there are concerns regarding the administration challenges of tarlatamab, which may affect its acceptance by clinicians and patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tarlatamab Shows Promise in SCLC. [2023]

Tarlatamab, a bispecific T-cell engager targeting DLL3 in small-cell lung cancer (SCLC), showed a manageable safety profile with 90.7% of patients experiencing treatment-related adverse events, including cytokine release syndrome in 52% of patients.

The treatment demonstrated an objective response rate of 23.4% and a median duration of response of 12.3 months, indicating promising antitumor activity in heavily pretreated SCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study. Paz-Ares, L., Champiat, S., Lai, WV., et al.[2023]

In a phase 2 trial involving 220 patients with previously treated small-cell lung cancer, tarlatamab demonstrated significant antitumor activity, with an objective response rate of 40% in the 10-mg group and 32% in the 100-mg group, indicating its potential as an effective treatment option.

The treatment was generally well-tolerated, with the most common side effects being cytokine-release syndrome, which was mostly mild (grade 1 or 2), and only 3% of patients discontinued due to treatment-related adverse events, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. Ahn, MJ., Cho, BC., Felip, E., et al.[2023]

Delta-like ligand 3 (DLL3) is a promising therapeutic target in small cell lung cancer (SCLC) due to its high expression in SCLC tumors and low expression in normal tissues, which may reduce treatment-related toxicities.

Several DLL3-targeted therapies, including the antibody-drug conjugate rovalpituzumab tesirine and bispecific T cell engager AMG 757, are being developed and show potential for improving treatment outcomes in patients with recurrent or refractory SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DLL3: an emerging target in small cell lung cancer. Owen, DH., Giffin, MJ., Bailis, JM., et al.[2020]

AMG 757 demonstrated strong antitumor activity against small-cell lung cancer (SCLC) by effectively targeting DLL3, leading to significant tumor regression and complete responses in mouse models, even in cases with low DLL3 expression.

The treatment was well tolerated in nonhuman primates, showing no adverse effects at the highest tested dose, and its extended half-life suggests it could allow for less frequent dosing in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer. Giffin, MJ., Cooke, K., Lobenhofer, EK., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40280845/

Real-World Outcomes of Tarlatamab in Small Cell Lung ... Tarlatamab is a promising treatment option for heavily pretreated small cell lung cancer patients. We observed higher rates of CRS and ICANS during the first ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2307980

Tarlatamab for Patients with Previously Treated Small-Cell ... Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04885998

AMG 757 and AMG 404 in Subjects With Small Cell Lung ... A combination RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an maximum tolerated dose (MTD).

4. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-472794

Taking a Bite Out of Small Cell Lung Cancer By Leveraging ... Tarlatamab is a bispecific T-cell engager (BiTE) that binds to delta-like ligand-3 (DLL3) on small cell lung cancer (SCLC) cells and cluster of differentiation ...

5. amgen.com amgen.com/newsroom/press-releases/2025/06/imdelltra-significantly-reduced-risk-of-death-by-40-in-small-cell-lung-cancer-patients

IMDELLTRA® SIGNIFICANTLY REDUCED RISK OF ... IMDELLTRA (tarlatamab-dlle) reduced the risk of death by 40% and significantly extended median overall survival (OS) by more than five months compared to ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8088

Real-world efficacy and safety of tarlatamab in patients with ... We report a real-world case series of safety and efficacy data for patients treated with standard of care tarlatamab at MD Anderson Cancer Center.

7. sciencedirect.com sciencedirect.com/science/article/pii/S152573042500052X

Real-World Outcomes of Tarlatamab in Small Cell Lung ... In conclusion, tarlatamab showed promising antitumor activity in a heavily pretreated, real-world ES-SCLC population. However, we observed higher rates of CRS ...