Tarlatamab for Small Cell Lung Cancer

(DeLLphi-309 Trial)

Recruiting at 99 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tarlatamab for small cell lung cancer (SCLC) that has progressed or returned after initial treatment. The goal is to determine how effectively tarlatamab stops or shrinks the cancer. Participants will receive one of three different doses of tarlatamab to identify the most effective dose. Those who have experienced a return or worsening of SCLC after one round of platinum-based chemotherapy and have a measurable tumor might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that tarlatamab has been tested for safety in people with small cell lung cancer (SCLC). In one study, a 10-mg dose of tarlatamab given every two weeks showed promising results, with patients experiencing lasting benefits and good survival rates, suggesting it might be well-tolerated.

A report from the MD Anderson Cancer Center shared real-world safety data for tarlatamab, supporting its general safety and a favorable balance between risks and benefits for treating SCLC.

Additionally, tarlatamab is approved for use in certain cases of extensive-stage SCLC after chemotherapy, indicating it has met safety standards for that condition. Overall, these findings suggest that tarlatamab is considered safe for use in humans, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Tarlatamab is unique because it represents a novel approach to treating small cell lung cancer (SCLC) by targeting a specific protein called delta-like ligand 3 (DLL3), which is commonly found on SCLC cells. Unlike traditional chemotherapy or radiation, which broadly attack cancer cells and can harm healthy cells, Tarlatamab is designed as a "bispecific T-cell engager" that directs the body's own immune cells to specifically attack cancer cells expressing DLL3. This targeted mechanism has the potential to improve effectiveness while reducing side effects, making researchers excited about its promise in offering a more precise treatment option for SCLC.

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

Research has shown that tarlatamab is a promising treatment for small cell lung cancer (SCLC), particularly for patients who have already tried other treatments. In one study, tarlatamab helped nearly half of the patients by either shrinking their cancer or keeping it stable. Another study found that patients who received tarlatamab lived longer than those who received traditional chemotherapy. Tarlatamab works by helping the body's immune cells, called T-cells, to find and fight cancer cells. This trial will evaluate different doses of tarlatamab, with participants receiving one of three doses. These findings suggest that tarlatamab could be an effective option for treating SCLC. ^{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 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

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

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sciencedirect.com

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

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Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes

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pubmed.ncbi.nlm.nih.gov

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Safety and activity of tarlatamab in combination with a PD ...

We evaluated the safety and activity of tarlatamab in combination with atezolizumab or durvalumab as first-line maintenance therapy in patients with extensive- ...

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ascopubs.org

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We report a real-world case series of safety and efficacy data for patients treated with standard of care tarlatamab at MD Anderson Cancer Center.

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These studies showed a good benefit–risk profile for tarlatamab in previously-treated small-cell lung cancer (SCLC), leading to global ...

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Tarlatamab, a bispecific T-cell engager, is approved for use in extensive-stage SCLC after progression on a platinum-based chemotherapy on the basis of the ...