Tarlatamab Combo for Small Cell Lung Cancer

Not currently recruiting at 61 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)

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety of a new treatment combination for individuals with extensive-stage small cell lung cancer (ES-SCLC). It combines tarlatamab, an experimental treatment, with other drugs such as atezolizumab and carboplatin to evaluate their combined effectiveness. The trial includes different groups testing various drug combinations. It suits those diagnosed with ES-SCLC who have not yet received systemic treatment. As a Phase 1 trial, this research aims to understand 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, if you are on systemic steroid therapy or any immunosuppressive therapy, you must stop these at least 7 days before starting the study treatment.

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

Research shows that combining tarlatamab with other treatments is generally safe. For the combination of tarlatamab, atezolizumab, carboplatin, and etoposide, studies report a good safety record and a 71% response rate in patients with small cell lung cancer. This indicates the treatment is usually well-tolerated, with manageable side effects.

The combination of tarlatamab and atezolizumab also demonstrates a positive safety profile. Previous studies have shown good safety results in patients who have already received treatment for small cell lung cancer.

Similarly, the tarlatamab and durvalumab combination appears safe, with encouraging results in small cell lung cancer patients.

Overall, these combinations remain in early testing, focusing mainly on safety. So far, data suggests they are generally safe and tolerable. However, like any treatment, side effects can occur, so discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they uniquely combine immunotherapy and chemotherapy to tackle small cell lung cancer. While standard treatments often rely on chemotherapy alone, this study explores using Tarlatamab, an investigational bispecific antibody, in combination with established drugs like Atezolizumab and Durvalumab, both of which are immune checkpoint inhibitors. These combinations aim to enhance the body's immune response against cancer cells. This approach could potentially improve the effectiveness of the treatment and provide a new avenue for patients who have limited options with traditional therapies.

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

Research has shown that combining tarlatamab with atezolizumab, carboplatin, and etoposide, which participants in this trial may receive, may effectively treat small cell lung cancer. In previous studies, 71% of patients responded to this combination, with many experiencing tumor shrinkage. Another treatment option in this trial is the combination of tarlatamab and atezolizumab, which has been shown to extend the time patients live with the disease before it worsens. Additionally, tarlatamab with durvalumab, another treatment arm in this trial, shows promise, with a response rate of 42.9%. These treatments aim to help patients live longer and manage their cancer more effectively. ^{3 6 7 8 9}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Adults with untreated Extensive Stage Small Cell Lung Cancer (ES-SCLC) can join this trial. They should have had no prior systemic treatment for ES-SCLC, may have treated brain metastases if stable, and must be generally healthy with good organ function and performance status (ECOG 0-1). People who've had major surgery recently, other cancers within 2 years, severe immune reactions to cancer immunotherapy, active autoimmune diseases needing treatment or any form of immunosuppression are excluded.

Inclusion Criteria

I have brain metastases but have been treated and am not showing symptoms.

I have had treatment for early-stage small cell lung cancer.

My organs are functioning well.

Exclusion Criteria

I have an immune system disorder or have been on steroids or other immune-weakening medicines in the last week.

I am currently on IV antibiotics for an infection but can join the study once it's treated.

I have had immune-related inflammation of my colon.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Participants receive Tarlatamab in combination with Atezolizumab, Carboplatin, and Etoposide to assess safety and tolerability

8-12 weeks

Dose Expansion

Expansion of dose exploration with additional participants to further evaluate safety and efficacy

12-24 weeks

Maintenance

Participants continue treatment with Tarlatamab and Atezolizumab or Durvalumab to maintain response

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Carboplatin
• Durvalumab
• Etoposide
• Tarlatamab

Trial Overview

The study is testing the safety of a new drug called Tarlatamab combined with Carboplatin and Etoposide chemotherapy drugs plus a PD-L1 inhibitor like Durvalumab or Atezolizumab in patients. It's an early-phase trial to see how well participants tolerate this combination therapy as a first-line treatment for ES-SCLC.

How Is the Trial Designed?

Group I: Part 9: Dose Expansion Maintenance Experimental Treatment 2 Interventions

Expansion with Tarlatamab+Durvalumab

Group II: Part 8: Dose Expansion Maintenance Experimental Treatment 2 Interventions

Expansion of Part 5 with Durvalumab

Group III: Part 7: Dose Expansion Experimental Treatment 4 Interventions

Expansion of Part 1, 2, or 3 with Durvalumab

Group IV: Part 6: Dose Expansion Maintenance Experimental Treatment 4 Interventions

Expansion of Part 5 with Atezolizumab

Group V: Part 5: Dose Exploration Maintenance Experimental Treatment 4 Interventions

Tarlatamab+Atezolizumab

Group VI: Part 4: Dose Expansion Experimental Treatment 4 Interventions

Expansion of Part 1, Part 2, or Part 3 with Atezolizumab

Group VII: Part 3: Dose Exploration Combination Regimen 3 Experimental Treatment 4 Interventions

Tarlatamab+Atezolizumab+Carboplatin+Etoposide

Group VIII: Part 2: Dose Exploration Combination Regimen 2 Experimental Treatment 4 Interventions

Tarlatamab+Atezolizumab+Carboplatin+Etoposide

Group IX: Part 1: Dose Exploration Combination Regimen 1 Experimental Treatment 4 Interventions

Tarlatamab+Atezolizumab+Carboplatin+Etoposide

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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 SKYSCRAPER-02 study involving 490 patients with untreated extensive-stage small-cell lung cancer, the addition of tiragolumab to atezolizumab and chemotherapy did not significantly improve progression-free survival (PFS) or overall survival (OS).

The combination treatment was well tolerated, with similar rates of immune-mediated adverse events between the tiragolumab and control groups, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. Rudin, CM., Liu, SV., Soo, RA., et al.[2023]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

In a study of 124 patients with treatment-naïve, metastatic nonsquamous PD-L1-positive non-small cell lung cancer, the combination of atezolizumab with carboplatin and nab-paclitaxel showed significantly improved overall survival (19.9 months) and progression-free survival (8.5 months) compared to carboplatin and nab-paclitaxel alone (14.8 months and 5.1 months, respectively).

While the combination therapy had a higher incidence of manageable adverse events like neutropenia and anemia, it still demonstrated a tolerable safety profile, suggesting it could be an effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. Xu, B., Cheng, H., Li, K., et al.[2023]

In the IMpower133 study involving 394 patients with extensive-stage small-cell lung cancer, the addition of atezolizumab to carboplatin and etoposide significantly improved progression-free and overall survival without increasing the overall safety risks compared to the placebo.

While immune-related adverse events were more common in the atezolizumab group, the overall safety profile was comparable to the placebo, and patient-reported quality of life improved more significantly in the atezolizumab group, supporting its use as a new standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Mansfield, AS., Każarnowicz, A., Karaseva, N., et al.[2022]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

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 study of 65 patients with extensive-disease small-cell lung cancer, the combination of atezolizumab, carboplatin, and etoposide showed a high response rate of 73.8%, with 80.5% in elderly patients (median age 74 years).

Despite some significant hematological toxicities, such as decreased neutrophil counts in 61.1% of elderly patients, the treatment demonstrated acceptable safety and efficacy, suggesting it could be a preferred standard treatment for elderly patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. Shiono, A., Imai, H., Wasamoto, S., et al.[2023]

Tiragolumab, a TIGIT inhibitor, shows promise in treating solid cancers, particularly non-small cell lung cancer, based on results from phase I and II trials.

The combination of tiragolumab with the PD-L1 inhibitor atezolizumab has demonstrated statistically significant efficacy in multiple solid tumors, suggesting a potential new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiragolumab Impresses in Multiple Trials. [2021]

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 study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

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