Tarlatamab for Small Cell Lung Cancer

(DeLLphi-306 Trial)

Recruiting at 248 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

Trial Summary

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.

What data supports the effectiveness of the drug Tarlatamab for small cell lung cancer?

Research shows that Tarlatamab, a drug that helps the body's immune cells attack cancer cells, has shown promising results in patients with small cell lung cancer, especially those whose cancer returned after other treatments. It targets a specific protein found on cancer cells, which helps the immune system recognize and destroy them. ^{1 2 3 4 5}

How is the drug Tarlatamab different from other treatments for small cell lung cancer?

Tarlatamab is unique because it is a bispecific T-cell engager that targets the protein delta-like ligand 3 (DLL3), which is highly expressed in small cell lung cancer cells but not in normal cells. This drug works by binding to both DLL3 and CD3, leading to the destruction of cancer cells by the body's own T-cells, offering a novel approach compared to traditional chemotherapy and radiotherapy. ^{1 2 3 4 6}

What is the purpose of this trial?

The primary objective of this study is to compare the efficacy of tarlatamab with placebo as assessed by progression free survival (PFS).

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Tarlatamab Shows Promise in SCLC. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer. [2023]

5. United States 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

DLL3: an emerging target in small cell lung cancer. [2020]