Tarlatamab for Small Cell Lung Cancer

Recruiting at 43 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)

269 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing tarlatamab, a special medicine, in people with Small Cell Lung Cancer. Tarlatamab helps the immune system find and destroy cancer cells.

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.

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 patients whose cancer had progressed after other treatments. In early trials, it demonstrated strong antitumor activity, suggesting it could be an effective option for this aggressive cancer. ^{1 2 3 4 5}

What safety data exists for Tarlatamab (AMG 757) in humans?

Tarlatamab, also known as AMG 757, has been tested in a phase 1 trial for small-cell lung cancer, showing promising activity. However, the research does not provide specific details on safety or side effects in humans. ^{1 2 3 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 a protein called delta-like ligand 3 (DLL3) on cancer cells and CD3 on T-cells, helping the immune system directly attack the cancer. This mechanism is different from traditional chemotherapy or other immunotherapies, making it a novel option for patients whose cancer has progressed after other treatments. ^{1 2 3 8 9}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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]

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 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]

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]

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. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. [2022]

5. 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]

6. United States 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. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. [2020]

8. United States 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). [2022]

9. 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]