Tarlatamab Combo for Small Cell Lung Cancer

Recruiting at 51 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

184 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called tarlatamab combined with treatments that help the immune system fight cancer, and sometimes with chemotherapy. It targets cancer patients who need new treatment options. Tarlatamab attacks cancer cells directly, while other treatments boost the immune response or kill 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, if you are on systemic steroid therapy or any immunosuppressive therapy, you must stop these at least 7 days before starting the study treatment.

What data supports the effectiveness of the drug combination for small cell lung cancer?

Research shows that adding atezolizumab to carboplatin and etoposide significantly improves overall survival and progression-free survival in patients with extensive-stage small-cell lung cancer compared to chemotherapy alone. ^{1 2 3 4 5}

Is the Tarlatamab Combo for Small Cell Lung Cancer safe for humans?

The combination of atezolizumab, carboplatin, and etoposide has been studied for safety in patients with extensive-stage small-cell lung cancer, showing a manageable safety profile with reported adverse events (side effects) in clinical trials. ^{2 6 7 8 9}

What makes the Tarlatamab Combo treatment unique for small cell lung cancer?

The Tarlatamab Combo treatment is unique because it includes tarlatamab, a first-of-its-kind bispecific T-cell engager that targets DLL3, a protein commonly found in small cell lung cancer, and helps the immune system attack cancer cells. This approach is different from standard treatments, which typically involve chemotherapy and immunotherapy without targeting DLL3. ^{1 2 4 10 11}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. [2023]

3. 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]

4. United States pubmed.ncbi.nlm.nih.gov

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

6. England 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. [2022]

7. Germany 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Tiragolumab Impresses in Multiple Trials. [2021]

9. England 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Tarlatamab Shows Promise in SCLC. [2023]

11. 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]