Tarlatamab for Lung Cancer

(DeLLphi-308 Trial)

Recruiting at 28 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

100 Participants Needed

Trial Summary

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.

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

Research shows that Tarlatamab, a drug that helps the body's immune cells attack cancer cells, has shown promising results in treating small-cell lung cancer, especially in patients whose cancer returned after other treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

The primary objective of this study is to evaluate the safety and tolerability of subcutaneous (SC) tarlatamab.

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: 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 II: 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

Findings from Research

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]

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]

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]

References

1. 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]

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

Tarlatamab Shows Promise in SCLC. [2023]

3. 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]

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

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

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

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