Tarlatamab for Small Cell Lung Cancer

(DeLLphi-309 Trial)

Recruiting at 35 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amgen

Must not be taking: Immunosuppressants, Corticosteroids, Chemotherapy, others

Disqualifiers: NSCLC, Autoimmune disease, Infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

240 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial requires that you stop any current anti-cancer therapy, such as chemotherapy, immunotherapy, or targeted therapy, before joining. Additionally, you should not be on systemic corticosteroid therapy or any other immunosuppressive therapy within 7 days prior to the first dose. If you are on any other medications, the protocol does not specify, so it's best to discuss with the trial team.

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

Tarlatamab has shown promising activity in patients with small cell lung cancer whose disease had progressed after other treatments, according to early phase trials. It works by engaging the body's immune cells to target and destroy cancer cells, specifically those expressing a protein called delta-like ligand 3 (DLL3). ^{1 2 3 4 5}

Is Tarlatamab safe for humans?

Tarlatamab has been studied in a phase I trial for small cell lung cancer, which is an early stage of testing that primarily assesses safety. While the study shows promise, it does not provide detailed safety data, and questions remain about its administration. ^{1 2 4 6 7}

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 delta-like ligand 3 (DLL3) protein, which is often found in small cell lung cancer. This drug works by binding to both DLL3 on cancer cells and CD3 on T-cells, helping the immune system to attack the cancer. ^{1 2 3 4 7}

What is the purpose of this trial?

The primary objective of this study is to describe the antitumor activity of tarlatamab in participants with small cell lung cancer (SCLC).

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for adults with small cell lung cancer (SCLC) that has gotten worse or come back after one platinum-based treatment. They must be able to do daily activities with little help (ECOG PS of 0 or 1), expected to live at least 12 weeks, and have organs working well enough as per the study's rules.

Inclusion Criteria

My small cell lung cancer has been confirmed and has worsened or returned.

Participant has provided informed consent prior to initiation of any study specific activities/procedures.

My cancer returned or worsened after one platinum-based treatment.

Exclusion Criteria

I have a lung condition not caused by an infection.

My cancer has spread to the lining of my brain and spinal cord.

My NSCLC has changed into small cell lung cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tarlatamab by intravenous infusion in one of three dosing regimens

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tarlatamab

Trial Overview The trial is testing Tarlatamab's ability to fight SCLC. It's an open-label study, meaning everyone knows what treatment they're getting, and it randomly assigns participants to different dosing schedules of Tarlatamab across multiple centers.

Participant Groups

Group I: Treatment Arm C: Dose 3 Tarlatamab Experimental Treatment 1 Intervention

Participants will receive dose 3 of Tarlatamab by IV infusion during the treatment period.

Group II: Treatment Arm B: Dose 2 Tarlatamab Experimental Treatment 1 Intervention

Participants will receive dose 2 of Tarlatamab by IV infusion during the treatment period.

Group III: Treatment Arm A: Dose 1 Tarlatamab Experimental Treatment 1 Intervention

Participants will receive dose 1 of Tarlatamab by intravenous (IV) infusion during the treatment period.

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 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]

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

This ongoing phase II clinical trial is evaluating the combination of serplulimab with chemotherapy (etoposide and carboplatin) in 36 patients with transformed small cell lung cancer (T-SCLC) that originated from EGFR-mutant non-small cell lung cancer (NSCLC).

The primary goal of the study is to assess progression-free survival, with secondary goals including overall survival and safety, addressing the urgent need for effective treatments in this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study. Huang, J., Zhang, XH., Cai, Y., et al.[2023]

References

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

Tarlatamab Shows Promise in SCLC. [2023]

2. 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]

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

A Randomized, Placebo-Controlled, Phase 1b/2 Study of Rilotumumab or Ganitumab in Combination With Platinum-Based Chemotherapy as First-Line Treatment for Extensive-Stage Small-Cell Lung Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

What's new in small cell lung cancer - extensive disease? An overview on advances of systemic treatment in 2016. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study. [2023]