Tarlatamab + AMG 404 for Small Cell Lung Cancer

Recruiting at 16 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

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new combination of two drugs to see if they are safe and to determine the best dose. It likely targets patients who need new treatment options. The drugs are expected to work together to improve treatment outcomes.

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.

What data supports the effectiveness of the drug Tarlatamab for Small Cell Lung Cancer?

Research shows that Tarlatamab, which targets a protein called DLL3 found in most small cell lung cancer tumors, has shown promising results in early trials for patients whose cancer returned after other treatments. ^{1 2 3 4 5}

Is Tarlatamab (AMG 757) safe for humans?

Tarlatamab, also known as AMG 757, has been tested in early-phase studies for small cell lung cancer and has shown promising activity. However, the research does not provide detailed safety data, so it's important to discuss potential risks with your healthcare provider. ^{1 2 3 4 5}

How is the drug Tarlatamab unique for treating small cell lung cancer?

Tarlatamab is unique because it is a bispecific T-cell engager that targets the DLL3 protein, which is commonly found on small cell lung cancer cells but not on normal cells. This allows the drug to direct the body's immune cells to attack the cancer cells specifically, offering a novel approach compared to traditional treatments. ^{1 2 3 4 5}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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]

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]

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. 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]

5. England 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). [2023]