Tarlatamab for Small Cell Lung Cancer

Not currently recruiting at 49 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, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies by part (e.g., 24-hour or 8-hour monitoring)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tarlatamab (also known as AMG 757) for individuals with small cell lung cancer (SCLC) that has returned or worsened after standard treatment. The trial aims to assess the safety and effectiveness of tarlatamab alone and in combination with other strategies, such as pembrolizumab (another cancer drug) or additional monitoring methods. Individuals whose SCLC has returned or worsened after a platinum-based treatment might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific requirements about the timing of prior anti-cancer therapies and certain treatments, so it's best to discuss your current medications with the trial team.

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

Research has shown that tarlatamab is generally safe for people with small cell lung cancer. In earlier studies, patients who had tried many treatments responded well to tarlatamab over an extended period, suggesting its promise in terms of safety. Another study found that the side effects were manageable, meaning they were not severe and could be controlled or treated.

This trial tests tarlatamab alone and with pembrolizumab, another cancer treatment drug. Previous research has not identified serious safety issues with these combinations. Overall, the treatment appears well-tolerated, meaning most people can take it without serious problems. Since this is an early-phase trial, the main goal is to understand the treatment's safety and how it works in the body. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for small cell lung cancer, which often include chemotherapy and immunotherapy, Tarlatamab offers a fresh approach by harnessing the body's immune system in a novel way. Researchers are excited about Tarlatamab because it targets a specific protein called DLL3, which is present in most small cell lung cancer cells but not in healthy tissues. This targeted action could potentially result in more effective treatment with fewer side effects. Additionally, Tarlatamab can be administered with innovative strategies, such as in outpatient settings with digital monitoring, making it more convenient for patients. These unique features set Tarlatamab apart from existing options and provide hope for better outcomes in treating this aggressive cancer.

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

Research has shown that tarlatamab could be a promising treatment for small cell lung cancer (SCLC), particularly for patients who haven't responded to other treatments. In earlier studies, tarlatamab helped shrink tumors for an extended period. This trial includes several treatment arms, such as tarlatamab monotherapy and tarlatamab combined with pembrolizumab. In previous studies, patients who received tarlatamab lived for an average of 13.6 months, longer than those who received standard chemotherapy. Additionally, studies found that 63% of patients experienced a partial response, with their tumors shrinking, when given higher doses. Although some side effects, like cytokine release syndrome (an overreaction of the immune system), were noted, the treatment shows potential benefits for SCLC patients. ^{1 2 6 7 8}

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 that's come back or didn't respond after chemo can join. They must have stable brain metastases, good organ function, and an ECOG status of 0-2. No recent immunosuppressants, untreated brain issues, severe immune reactions to cancer drugs, active infections or major surgery within the last month.

Inclusion Criteria

My organs are functioning well.

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

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have a lung condition not caused by an infection.

I have not taken steroids or immunosuppressants in the last 7 days.

I have not had any other cancer besides my current one in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tarlatamab monotherapy or in combination with other therapies, with monitoring for safety and tolerability

Varies by part (e.g., 24-hour or 8-hour monitoring)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• AMG 757

Trial Overview

The trial is testing Tarlatamab's safety and how the body processes it in adults with SCLC. It includes strategies to manage side effects (CRS Mitigation) and compares Tarlatamab with Pembrolizumab—a known treatment.

How Is the Trial Designed?

Group I: Part G Experimental Treatment 1 Intervention

Tarlatamab additional dosing schedule Optional wearable digital device substudy (US sites only)

Group II: Part F Experimental Treatment 1 Intervention

Tarlatamab administered in outpatient infusion centers with 8-hour monitoring Optional wearable digital device substudy (US sites only)

Group III: Part E Experimental Treatment 1 Intervention

Tarlatamab administration with 24-hour monitoring

Group IV: Part D Experimental Treatment 2 Interventions

Tarlatamab with additional CRS mitigation strategies

Group V: Part C Experimental Treatment 2 Interventions

Tarlatamab with Pembrolizumab

Group VI: Part A Experimental Treatment 1 Intervention

Tarlatamab monotherapy

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, 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 combination of the anti-PD-1 antibody budigalimab and the antibody-drug conjugate Rova-T was found to be tolerated in 31 patients with previously treated small cell lung cancer (SCLC), with common side effects including pleural effusion, fatigue, and cough.

This combination therapy showed an overall response rate of 24.1%, with one complete response and six partial responses, indicating promising efficacy despite the discontinuation of Rova-T's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Calvo, E., Spira, A., Miguel, M., et al.[2022]

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]

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]

In a study involving 403 patients with extensive-stage small-cell lung cancer, adding atezolizumab to carboplatin and etoposide significantly improved overall survival (OS) from 10.3 months to 12.3 months compared to placebo, indicating its efficacy as a first-line treatment.

The addition of atezolizumab showed a tolerable safety profile and provided benefits regardless of patients' PD-L1 or blood-based tumor mutational burden status, suggesting it can be effective across different patient biomarker profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). Liu, SV., Reck, M., Mansfield, AS., et al.[2022]

In a phase 2 study involving patients with untreated advanced non-small-cell lung cancer, the addition of panitumumab to carboplatin and paclitaxel did not improve the time to progression (TTP) compared to carboplatin and paclitaxel alone, with TTP being 18.1 weeks for the combination and 23.0 weeks for the control group.

While the combination treatment was associated with manageable and predictable toxicities, including skin issues and gastrointestinal symptoms, it did not enhance the overall efficacy, as indicated by similar progression-free survival and objective response rates between the two treatment arms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 randomized trial of paclitaxel and carboplatin with or without panitumumab for first-line treatment of advanced non-small-cell lung cancer. Crawford, J., Swanson, P., Schwarzenberger, P., et al.[2018]

Combining anti-PD-1 or anti-PD-L1 immunotherapy with platinum-based chemotherapy significantly improves outcomes for patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), based on a systematic review of 9 randomized studies.

While immune-mediated adverse events (AEs) and infusion reactions were more common with the combination therapy, there were no unexpected toxicities, indicating that the treatment is generally safe and manageable with appropriate monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. Hoffner, B., Leighl, NB., Davies, M.[2020]

Citations

1.

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 ...

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2307980

Tarlatamab for Patients with Previously Treated Small-Cell ...

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

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.8510

Updated results from a phase 1 study of AMG 757, a half- ...

Encouraging anti-tumor activity was seen across dose ranges, with ongoing unconfirmed PR in 5/8 pts (63%) at the highest DL. The study is ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40454646/

Tarlatamab in Small-Cell Lung Cancer after Platinum- ...

Treatment with tarlatamab resulted in significantly longer overall survival than chemotherapy (median, 13.6 months [95% confidence interval {CI} ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06830694?cond=small+cell+lung+cancer&term=atezolizumab&aggFilters=status%3A%2Cphase%3A

Clinical Trial for Safety and Effectiveness Evaluation of ...

However, median progression-free survival (PFS) of both study was only 5.2 months and 5.1 months, despite the objective response rate showing 60.2% and 79%.

6.

aacrjournals.org

aacrjournals.org/clincancerres/article/27/5/1526/267119/AMG-757-a-Half-Life-Extended-DLL3-Targeted

AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T ...

A half-life extended, DLL3-targeted bispecific T-cell engager, shows high potency and sensitivity in preclinical models of small-cell lung cancer.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04885998

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

A combination RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an maximum tolerated dose (MTD).

8.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36689692/

Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell ...

In patients with heavily pretreated SCLC, tarlatamab demonstrated manageable safety with encouraging response durability.