Tarlatamab + Durvalumab for Lung Cancer

(DeLLphi-305 Trial)

Not currently recruiting at 286 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must be taking: Platinum-etoposide, Durvalumab

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disorders, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two drugs, tarlatamab and durvalumab, helps people with extensive-stage small-cell lung cancer (ES-SCLC) live longer compared to using durvalumab alone. Candidates who have responded well to an initial round of chemotherapy with durvalumab and whose cancer hasn't progressed might be suitable for this study. The trial includes two groups: one receiving only durvalumab and the other receiving both tarlatamab and durvalumab. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot be on systemic corticosteroids or other immunosuppressive therapy within 14 days before starting the study treatment. It's best to discuss your specific medications with the study team.

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

Research has shown that using tarlatamab and durvalumab together is generally safe for patients with small-cell lung cancer. Studies found that patients tolerated this treatment well, meaning the benefits outweighed the risks. These positive results have led to approvals for its use in certain conditions worldwide.

Durvalumab, one of the drugs in this study, already has FDA approval for some types of cancer, supporting its safety. While some patients may experience side effects, research indicates that these treatments are safe when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Tarlatamab combined with Durvalumab for lung cancer because these treatments work together in a unique way to boost the immune system's ability to fight cancer. Unlike standard treatments that often target cancer cells directly, Tarlatamab is a bispecific T-cell engager, which means it helps the body's T-cells recognize and attack cancer cells more effectively. When paired with Durvalumab, an immune checkpoint inhibitor that helps block signals preventing the immune system from attacking cancer, this combination has the potential to offer a more powerful and targeted approach to treating lung cancer. This dual action could lead to improved outcomes for patients by enhancing the body's natural defenses against the disease.

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

Research has shown that tarlatamab, when combined with durvalumab, may improve survival rates for small-cell lung cancer (SCLC). In this trial, some participants will receive both tarlatamab and durvalumab. Previous studies found that tarlatamab significantly increased overall survival in patients who had already received treatment for SCLC. Additionally, combining tarlatamab with a PD-L1 inhibitor like durvalumab demonstrated a good balance between benefits and risks for these patients. This evidence suggests that the combination could effectively extend life in SCLC. Meanwhile, other participants in this trial will receive durvalumab alone to compare its effectiveness. ^{2 6 7 8 9}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults with extensive-stage small-cell lung cancer who've had 3-4 cycles of specific chemo and a drug called durvalumab without their disease getting worse. They should be expected to live at least 12 more weeks, have resolved treatment side effects (except hair loss or tiredness), and good organ function. People with active brain metastases or poor physical status can't join.

Inclusion Criteria

You are expected to live for at least 12 more weeks.

Criterion: You are not allowed to participate.

You have agreed to take part in the study before it starts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tarlatamab every 2 weeks and durvalumab every 4 weeks, or durvalumab alone every 4 weeks

Until disease progression or unacceptable toxicity

Bi-weekly and monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Tarlatamab

Trial Overview

The study aims to see if adding tarlatamab to durvalumab improves overall survival compared to using durvalumab alone in patients who have already received initial treatments for extensive-stage small-cell lung cancer.

How Is the Trial Designed?

Group I: Tarlatamab in Combination With Durvalumab Experimental Treatment 2 Interventions

Participants will receive tarlatamab once every 2 weeks (Q2W) and durvalumab once every 4 weeks (Q4W).

Group II: Durvalumab Alone Active Control 1 Intervention

Participants will receive durvalumab Q4W alone.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

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

In the phase III PACIFIC trial, durvalumab treatment led to a low incidence of immune-mediated adverse events (imAEs), with any-grade immune-mediated pneumonitis occurring in 9.4% of patients and grade 3/4 imAEs in only 3.4%.

Despite the occurrence of imAEs being more common with durvalumab compared to placebo, these events were generally manageable with treatments like corticosteroids, indicating that the benefits of the PACIFIC regimen outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. Naidoo, J., Vansteenkiste, JF., Faivre-Finn, C., et al.[2022]

In a study of 81 patients with unresectable locally advanced non-small cell lung cancer (NSCLC), those with high tumor mutational burden (TMB-high) showed significantly better outcomes, including lower local-regional failure rates (9% vs 51%) and improved progression-free survival (66% vs 27%) compared to TMB-low patients.

The study suggests that TMB status could be a valuable biomarker for personalizing treatment strategies, as it was the only factor significantly associated with local-regional failure and progression-free survival after treatment with chemoradiation and adjuvant durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. Lebow, ES., Shepherd, A., Eichholz, JE., et al.[2023]

Durvalumab has been approved for use in patients with locally advanced PD-L1-positive non-small cell lung cancer (NSCLC) after chemoradiotherapy, based on its efficacy demonstrated in the PACIFIC trial and subsequent analysis of 211 patients in the Expanded Access Program (EAP).

In the EAP, 126 patients who received durvalumab were included, some of whom had oligometastatic disease and a history of autoimmune conditions, indicating that durvalumab may be effective and safe for a broader patient population than previously studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP. Faehling, M., Schumann, C., Christopoulos, P., et al.[2020]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

In a phase Ib study involving 136 patients, durvalumab (Du) combined with tremelimumab (Tr) and standard platinum-doublet chemotherapy was found to be safe, with most drug-related adverse events being mild (≤ grade 2) and primarily due to chemotherapy.

Among 73 patients with non-small cell lung cancer (NSCLC), the treatment achieved a 51% objective response rate, with a median progression-free survival of 6.5 months and overall survival of 19.8 months, indicating promising efficacy comparable to other immunotherapy and chemotherapy combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. Juergens, RA., Hao, D., Ellis, PM., et al.[2021]

In a study of 121 patients with stage III non-small cell lung cancer treated with durvalumab, those with over 50% PD-L1 expression had significantly better outcomes, with a 1-year survival rate of 97% compared to 73% and 78% for lower expression groups.

Higher PD-L1 expression (>50%) was strongly associated with improved progression-free survival and overall survival, indicating that PD-L1 levels could be a key factor in predicting the effectiveness of durvalumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. Jazieh, K., Gad, M., Saad, A., et al.[2022]

Durvalumab, a PD-L1 inhibitor, has shown promising results in increasing progression-free survival and objective response rates in patients with inoperable and locally advanced stage III non-small cell lung cancer, based on interim results from a phase III trial.

The significant benefits observed suggest that durvalumab could potentially become the standard treatment for these patients in the United States.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Promising for NSCLC. [2019]

In a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., et al.[2022]

Citations

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DeLLphi-305 (SCLC)

This clinical trial aims to see how safe and effective tarlatamab is at treating patients with small-cell lung cancer (SCLC).

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Previous studies have shown tarlatamab prolongs overall survival in the second-line SCLC setting. In the DeLLphi-303 trial, investigators ...

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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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IMDELLTRA demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) compared to local standard-of-care (SOC) ...

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The main objective of the study is to compare the efficacy of tarlatamab in combination with durvalumab, carboplatin and etoposide to the combination of ...

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The primary objective of this study is to compare the efficacy of tarlatamab plus durvalumab with durvalumab alone on prolonging overall survival (OS).

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sciencedirect.com/science/article/abs/pii/S1470204525004802

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Press Release Details

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