Tarlatamab for Lung Cancer

(DeLLphi-308 Trial)

Recruiting at 38 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amgen

Must not be taking: Steroids

Disqualifiers: Brain metastases, Leptomeningeal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

220 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 for individuals with ES-SCLC (extensive-stage small cell lung cancer) that has returned or worsened after initial treatments. The main goal is to determine if tarlatamab is safe and tolerable when administered as an injection under the skin. Participants will assist researchers in identifying the best dose and exploring different dosing options. Candidates may qualify if their lung cancer has progressed after platinum-based therapy and they do not have untreated or symptomatic brain issues. As a Phase 1 trial, this research aims to understand how tarlatamab works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that tarlatamab has been studied for its safety in various contexts. One study found tarlatamab to be safe and effective in treating certain cancers, with some patients responding well. Another study focused on its use in small-cell lung cancer, showing promising survival rates and manageable safety issues.

Although tarlatamab is approved for treating extensive-stage small cell lung cancer, research continues to assess its safety. This current trial is in its early stages and primarily aims to evaluate the safety and tolerability of tarlatamab when administered as an injection under the skin. The trial is still gathering information on how well participants tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tarlatamab is unique because it uses a different approach to fighting lung cancer. Unlike traditional treatments like chemotherapy and radiation, which target rapidly dividing cells, Tarlatamab uses a bispecific T-cell engager (BiTE) technology. This means it helps the body’s immune system find and attack cancer cells more effectively. Researchers are excited about Tarlatamab because it offers a targeted way to engage the immune system, potentially leading to fewer side effects and improved outcomes for patients.

What evidence suggests that tarlatamab might be an effective treatment for lung cancer?

Research has shown that tarlatamab yields promising results for treating small cell lung cancer (SCLC). In studies, patients who received tarlatamab lived longer than those who received standard chemotherapy. Tarlatamab enhances the immune system's ability to find and destroy cancer cells more effectively. This trial will administer tarlatamab in different dosing regimens to evaluate its safety and effectiveness. In real-world use, patients previously treated for SCLC also experienced positive results with tarlatamab. These findings suggest that tarlatamab could be a viable option for people with this type of lung cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults over 18 with extensive stage small cell lung cancer (ES-SCLC) that's worsened after platinum-based treatment. They must be fairly active and healthy overall (ECOG status of 0 or 1), have good organ function, and be able to receive injections in the abdomen or thigh.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I may not have measurable cancer or available tumor tissue, but I have Amgen's approval to participate.

My small cell lung cancer returned after platinum-based treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Tarlatamab is administered as a subcutaneous injection to explore dosing

8-12 weeks

Dose Expansion

Tarlatamab is administered at the dose deemed safe and tolerable

8-12 weeks

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 study is testing the safety and how well people tolerate Tarlatamab when it's given as a subcutaneous injection, which means it's injected under the skin, typically in areas like the abdomen.

How Is the Trial Designed?

Group I: Part 3 Alternative Dosing Experimental Treatment 1 Intervention

Following the selection of a SC dosing regimen from Part 1 that will be used in Part 2 dose expansion, Part 3 may open to test alternative dosing of SC tarlatamab.

Group II: Part 2 Dose Expansion Experimental Treatment 1 Intervention

Following the selection of a SC dosing regimen in Part 1, tarlatamab will be administered in Part 2 at the dose deemed safe and tolerable in Part 1.

Group III: Part 1 Dose Exploration Experimental Treatment 1 Intervention

Tarlatamab will be administered as a SC injection in Part 1.

Tarlatamab is already approved in United States for the following indications:

Approved in United States as Imdelltra for:

• Extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy

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

BeOne Medicines

Industry Sponsor

Published Research Related to This Trial

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]

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]

The phase III POSEIDON trial demonstrated that a three-drug regimen combining the CTLA4 inhibitor tremelimumab, the PD-L1 inhibitor durvalumab, and chemotherapy significantly improves progression-free survival and overall survival in patients with metastatic non-small cell lung cancer compared to chemotherapy alone.

This study suggests that targeting multiple immune pathways with this combination therapy may enhance treatment effectiveness for lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Drug Regimen Bests Chemo in NSCLC. [2022]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06830694?cond=SCLC%20Transformed&rank=5

Study Details | NCT06830694 | Clinical Trial for Safety and ... T790M (36-50%), followed by MET amplification (10-19%). Interestingly, up to 3-5% of patients experience histological transformation into small cell lung cancer ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12459094/

Efficacy outcomes between tarlatamab and real-world ... The DeLLphi-301 trial of tarlatamab demonstrated promising survival among patients with extensive stage small-cell lung cancer (ES-SCLC), but it ...

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

Real-World Outcomes of Tarlatamab in Small Cell Lung ... Tarlatamab, a bispecific T-cell engager, has shown promising results in previously treated small cell lung cancer (SCLC) patients in the DeLLphi-300 and ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20120

Real world outcomes of patients treated with tarlatamab in ... Real-world safety and efficacy of tarlatamab in patients with small cell lung cancer or extrapulmonary small cell carcinoma.

5. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2502099

Tarlatamab in Small-Cell Lung Cancer after Platinum ... Treatment with tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169500225006932

A pharmacovigilance study based on the FAERS database Tarlatamab (Imdelltra, AMG757) has been approved for extensive-stage small cell lung cancer (ES-SCLC) treatment, yet post-marketing data remain ...

7. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06064500

Tarlatamab (AMG 757) Expanded Access Protocol for ... The primary objective of the study is to provide expanded access to and characterize the safety profile of tarlatamab in participants with advanced small cell ...

8. 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

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33203642/

AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific ... AMG 757 has a compelling safety and efficacy profile in preclinical studies making it a viable option for targeting DLL3-expressing SCLC ...

10. onclive.com onclive.com/view/tarlatamab-demonstrates-early-safety-and-activity-in-dll3-neuroendocrine-prostate-cancer

Tarlatamab Demonstrates Early Safety and Activity in ... Tarlatamab showed a 10.5% objective response rate in NEPC, with better outcomes in DLL3-positive tumors, achieving a 22.2% response rate. Common ...