Immunotherapy + Chemotherapy for Small Cell Lung Cancer

Recruiting at 140 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Immunodeficiency, Active CNS metastases, 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: 12 weeks

460 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new combination of immunotherapy and chemotherapy for patients with advanced lung cancer. The treatment uses two drugs to help the immune system fight cancer, along with standard chemotherapy to kill cancer cells. Researchers hope this new approach will improve survival compared to existing treatments.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any other form of immunosuppressive therapy, you must stop at least 7 days before the first dose of the study medication.

What data supports the effectiveness of the drug combination of Atezolizumab, Carboplatin, and Etoposide for treating small cell lung cancer?

Research shows that adding Atezolizumab to the chemotherapy drugs Carboplatin and Etoposide significantly improves survival rates for patients with extensive-stage small cell lung cancer compared to chemotherapy alone. This combination has become a standard first-line treatment option due to its effectiveness in prolonging life without worsening the quality of life. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemotherapy safe for treating small cell lung cancer?

The combination of atezolizumab (Tecentriq) with carboplatin and etoposide has been generally well tolerated in patients with extensive-stage small cell lung cancer, with no new safety concerns beyond those known for the individual drugs. Common side effects include blood-related issues, skin rash, and low thyroid function, but it did not negatively affect patients' quality of life. Pembrolizumab (Keytruda), another immunotherapy, can cause pneumonitis (lung inflammation) in a small percentage of patients. ^{1 6 7 8 9}

How does the drug Atezolizumab combined with chemotherapy differ from other treatments for small cell lung cancer?

Atezolizumab, when combined with carboplatin and etoposide, is unique because it is the first immune checkpoint inhibitor approved for extensive-stage small cell lung cancer, significantly improving survival compared to chemotherapy alone, without worsening quality of life. ^{1 7 10 11 12}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with a confirmed diagnosis of extensive-stage small cell lung cancer (ES-SCLC) who need first-line therapy. Participants must have a life expectancy over 3 months, agree to contraception if applicable, and not be pregnant or breastfeeding. Exclusions include severe allergies to study drugs, recent major surgery, active infections, certain medical conditions like CNS metastases or HIV, prior SCLC treatment, and recent live vaccines.

Inclusion Criteria

You have a cancer that can be measured using specific guidelines.

I am not pregnant, breastfeeding, and if able to have children, I use effective birth control or practice abstinence.

I have small cell lung cancer and need first-line therapy.

Exclusion Criteria

I have a history of or currently have a neurological disorder related to cancer.

I haven't had major surgery in the last 3 weeks and have recovered from any previous procedures.

I have received an organ or tissue transplant from another person.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 cycles of chemotherapy with either MK-7684A or atezolizumab in combination with etoposide and platinum, followed by maintenance therapy with MK-7684A or atezolizumab

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 60 months

Open-label extension (optional)

Participants benefiting from atezolizumab may continue on study and receive treatment with atezolizumab until discontinuation criteria are met

Treatment Details

Interventions

• Atezolizumab
• Carboplatin
• Cisplatin
• Etoposide
• Pembrolizumab

Trial Overview The trial tests pembrolizumab/vibostolimab co-formulation with etoposide/platinum chemotherapy against atezolizumab with the same chemo in treating ES-SCLC. The goal is to see if the new drug combo improves overall survival compared to the existing treatment option.

Participant Groups

Group I: Pembrolizumab/Vibostolimab Experimental Treatment 5 Interventions

Participants will receive 4 cycles (each cycle is 3 weeks) of a fixed-dose coformulation of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684A) every 3 weeks (Q3W), in combination with 100 mg/m\^2 etoposide, and platinum (Area Under the Curve (AUC) 5 mg/mL/min carboplatin or 75 mg/m\^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of MK-7684A Q3W until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.

Group II: Atezolizumab Active Control 5 Interventions

Participants will receive 4 cycles (each cycle is 3 weeks) of 1200 mg atezolizumab Q3W, in combination with 100 mg/m\^2 etoposide and platinum (AUC 5 mg/mL/min carboplatin or 75 mg/m\^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of atezolizumab Q3W until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.

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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

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 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]

Atezolizumab combined with carboplatin and etoposide was effective in treating a 75-year-old woman with advanced small cell lung cancer and an ECOG Performance Status of 2, leading to complete regression after 4 cycles of treatment.

Despite experiencing some adverse effects like anemia and thrombocytopenia, the patient's therapy was continued due to positive imaging results, highlighting the potential for immunochemotherapy in patients typically excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin. Dębczyński, M., Mojsak, D., Kuklińska, B., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

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 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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Combination treatments using platinum compounds and etoposide show median survival rates of 7 to 10 months for extensive-stage and 15 to 20 months for limited-stage small cell lung cancer, indicating their effectiveness in improving patient outcomes.

Adding paclitaxel to platinum/etoposide regimens has shown promising results in early studies, with good activity and manageable toxicity, and ongoing phase III trials aim to clarify its role in enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role and future prospects of paclitaxel in the treatment of small cell lung cancer. Hainsworth, JD., Greco, FA.[2015]

In the CASPIAN study involving 805 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of durvalumab and platinum-etoposide significantly improved overall survival compared to platinum-etoposide alone, with a median survival of 12.9 months versus 10.5 months.

However, adding tremelimumab to durvalumab and platinum-etoposide did not provide a significant survival benefit, indicating that durvalumab plus platinum-etoposide should be considered the new standard of care for first-line treatment of ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Goldman, JW., Dvorkin, M., Chen, Y., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. [2021]

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy in Small Cell Lung Cancer. [2020]

4. 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]

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

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

7. 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]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

The current role and future prospects of paclitaxel in the treatment of small cell lung cancer. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. [2021]

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

Atezolizumab plus carboplatin and etoposide in small cell lung cancer patients previously treated with platinum-based chemotherapy. [2022]