Tarlatamab + AMG 404 for Small Cell Lung Cancer

No longer recruiting at 17 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amgen

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Other malignancy, Brain metastases, Pneumonitis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with small cell lung cancer (SCLC) whose disease has progressed after at least one round of chemotherapy. The goal is to determine the safety of the combination of tarlatamab (also known as AMG 757) and AMG 404 and establish the best dose for future studies. Participants must have a confirmed SCLC diagnosis and have previously received a platinum-based chemotherapy regimen. The study seeks individuals with stable health, including treated brain metastases that meet specific criteria. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that tarlatamab, combined with AMG 404, is under study for safety in treating small cell lung cancer. Recent studies have shown promising results. However, some side effects, such as CRS (cytokine release syndrome) and ICANS (immune effector cell-associated neurotoxicity syndrome), have been reported. These immune system reactions can cause symptoms like fever or confusion.

The trial is in its early stages, focusing on finding the safest dose. This phase typically involves monitoring for any negative reactions. While some information on possible side effects exists, the trial aims to gather more data to understand how well participants tolerate the treatment.

In summary, although some evidence of side effects exists, the treatment is still under safety evaluation. Those interested in these initial findings should discuss with a healthcare provider to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Tarlatamab and AMG 404 for small cell lung cancer because they offer a novel approach compared to traditional chemotherapy and immunotherapy options. Tarlatamab is a bispecific T-cell engager, which means it can bring a patient's T-cells directly to the cancer cells, potentially enhancing the immune response more effectively. Meanwhile, AMG 404 is a PD-1 inhibitor that helps to prevent cancer cells from evading the immune system, potentially improving patient outcomes. This combination aims to create a powerful one-two punch against cancer cells, offering hope for those who might not respond well to existing treatments.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research has shown that tarlatamab, a treatment for small cell lung cancer (SCLC), yields promising results in extending patient survival. Studies suggest that tarlatamab significantly improves survival compared to standard treatments, with patients living longer than with other options. This trial explores the combination of tarlatamab with another drug, AMG 404, to determine if it can further enhance these benefits. Overall, these findings offer hope for people with SCLC, especially those who haven't found success with other treatments. ^{1 6 7 8 9}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Adults over 18 with Small Cell Lung Cancer (SCLC) that's worsened after platinum-based therapy can join. They must be fairly active (ECOG 0-1), have treated brain metastases meeting certain conditions, proper organ function, and no recent other cancers or major surgeries. Immune system issues, untreated brain problems, or prior similar treatments disqualify them.

Inclusion Criteria

I have had treatment for brain metastases and meet specific criteria.

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

I can carry out all my daily activities without help.

Exclusion Criteria

I have had an organ transplant.

I finished any palliative radiotherapy at least a week before starting tarlatamab.

I had severe side effects from immune therapy that stopped my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

The recommended phase 2 target dose of tarlatamab in combination with AMG 404 is estimated using a modified toxicity probability interval (mTPI-2) design.

Up to 28 days

Dose Expansion

Participants receive the RP2D of tarlatamab in combination with AMG 404 identified in Phase 1.

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 47 days after the last dose

What Are the Treatments Tested in This Trial?

Interventions

• AMG 404
• AMG 757
• Tarlatamab

Trial Overview

The trial is testing the safety and best dose of tarlatamab combined with AMG 404 in treating SCLC. It aims to find out how well patients tolerate this combination and establish a recommended dosage for further studies.

How Is the Trial Designed?

Group I: Phase 2: Dose Expansion Experimental Treatment 2 Interventions

Participants will receive the RP2D of tarlatamab in combination with AMG 404 identified in Phase 1 (dose exploration) of the study.

Group II: Phase 1: Dose Exploration Experimental Treatment 2 Interventions

The recommended phase 2 target dose (RP2D) of tarlatamab in combination with AMG 404 will be estimated using a modified toxicity probability interval (mTPI-2) design. A combination RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an maximum tolerated dose (MTD).

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

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]

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]

AMG 119, a CAR-T cell therapy targeting DLL3, shows promising results in patients with relapsed/refractory small cell lung cancer, demonstrating robust cellular expansion and long-lasting persistence.

The therapy has been found to be clinically safe and well tolerated, with no reported dose-limiting toxicities, marking a significant step towards CAR-T cell therapies for solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacology Profile of AMG 119, the First Chimeric Antigen Receptor T (CAR-T) Cell Therapy Targeting Delta-Like Ligand 3 (DLL3), in Patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC). Zhou, D., Byers, LA., Sable, B., 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]

Citations

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clinicaltrials.gov

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Clinical Review - Tarlatamab (Imdelltra) - NCBI Bookshelf

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amgen.com/newsroom/press-releases/2025/04/imdelltra-demonstrated-superior-overall-survival-in-small-cell-lung-cancer

IMDELLTRA® DEMONSTRATED SUPERIOR OVERALL ...

IMDELLTRA demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) compared to local standard-of-care (SOC) ...

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The study findings suggest that tarlatamab offers potential clinical benefits relative to comparator treatments.

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accessdata.fda.gov/drugsatfda_docs/nda/2024/761344Orig1s000MultidisciplineR.pdf

761344Orig1s000 - accessdata.fda.gov

... small cell lung cancer cell lines, tarlatamab resulted in upregulation of T cell ... outcomes of patients with small cell lung cancer ...

7.

pubmed.ncbi.nlm.nih.gov

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

Real-World Outcomes of Tarlatamab in Small Cell Lung ...

Conclusions: Tarlatamab is a promising treatment option for heavily pretreated small cell lung cancer patients. We observed higher rates of CRS and ICANS during ...

8.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/98/NCT04885998/Prot_000.pdf

Product: Tarlatamab (AMG 757), AMG 404 Protocol Number

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AMG 757 and AMG 404 in Subjects With Small Cell Lung ...

The main purpose of this study is to evaluate the safety, tolerability, and recommended phase 2 target dose of tarlatamab in combination with AMG 404.