Immunotherapy + Chemotherapy for Small Cell Lung Cancer

Not currently recruiting at 184 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with extensive-stage small cell lung cancer (ES-SCLC), a type of lung cancer that has spread widely. The researchers aim to determine if a new combination of drugs—pembrolizumab (an immunotherapy drug) and vibostolimab—with chemotherapy can extend patient survival compared to the current treatment option, atezolizumab (an immunotherapy drug) with chemotherapy. Participants will receive one of these treatments to identify which is more effective. Those with ES-SCLC who have not started first-line therapy might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking 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.

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

Research has shown that combining pembrolizumab and vibostolimab yields promising results in early studies for some lung cancers. These studies found that most patients tolerated the treatment well. However, possible side effects include tiredness, nausea, or changes in blood cell levels.

Atezolizumab, when combined with chemotherapy, has undergone more thorough study. The IMpower 133 trial found that this combination helped patients with extensive-stage small cell lung cancer live longer. The side effects were generally manageable, with common ones being tiredness, loss of appetite, and nausea.

Both treatments have shown potential in helping patients, but discussing any concerns or questions with healthcare providers is important. They can offer advice based on individual health needs and the details of the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to tackling small cell lung cancer (SCLC). Unlike traditional treatments, which typically include chemotherapy drugs like etoposide combined with platinum agents (carboplatin or cisplatin), the study introduces a combination of immunotherapies—pembrolizumab with vibostolimab and atezolizumab. Pembrolizumab and vibostolimab, as well as atezolizumab, are immune checkpoint inhibitors that help the immune system recognize and attack cancer cells more effectively. This mechanism of action is different from standard chemotherapy, which directly kills rapidly dividing cells, offering a potential new way to improve outcomes for patients with SCLC.

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

Research has shown that adding pembrolizumab and vibostolimab to chemotherapy has promising effects against tumors, particularly in non-small-cell lung cancer. This trial will evaluate the combination of pembrolizumab and vibostolimab with chemotherapy for small cell lung cancer. Atezolizumab, another treatment option in this trial, has been proven to extend survival in people with extensive-stage small cell lung cancer when combined with chemotherapy. Specifically, studies found that atezolizumab increased patients' survival to about 12.3 months on average. This trial compares both treatments to determine which one can extend life expectancy for people with this type of lung cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Pembrolizumab/Vibostolimab Experimental Treatment 5 Interventions

Participants will receive 4 cycles (each cycle is 3 weeks) of a fixed-dose coformulation (FDC) of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684A) every 3 weeks (Q3W) via intravenous (IV) infusion, 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 (200 mg vibostolimab/200 mg pembrolizumab FDC) Q3W via IV infusion, 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 via IV infusion, 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 (1200mg atezolizumab) Q3W via IV infusion 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

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1. tecentriq-hcp.com tecentriq-hcp.com/sclc/efficacy/clinical-trial-results.html

IMpower133 efficacy results in 1L ES-SCLC Adding TECENTRIQ® (atezolizumab) to carbo/etop significantly improved median PFS1. 5.2-month median PFS vs 4.3 months with placebo + carbo/etop (HR=0.77*; ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37871898/

The Real-World Outcome of First Line Atezolizumab in ... We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809064

First-Line Atezolizumab plus Chemotherapy in Extensive- ... Despite response rates of 60 to 65%, limited progress has been made in more than two decades; outcomes remain poor, with a median overall ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0169500223009170

Results of the IFCT-1905 CLINATEZO real-world study Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer. · Atezolizumab plus chemotherapy improves overall survival in 1st-line treatment of ...

5. tecentriq.com tecentriq.com/sclc/results/how-tecentriq-may-help.html

Imagine if you had more time to live your life More patients lived longer with TECENTRIQ + chemotherapy ... Median overall survival (OS) was 12.3 months for patients taking TECENTRIQ® (atezolizumab.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11880126/

Efficacy and safety analysis of atezolizumab continuation ... The IMpower 133 trial demonstrated that combining atezolizumab with chemotherapy significantly enhanced survival, establishing chemo-immunotherapy as the ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39306923/

Five-year survival in patients with extensive-stage small ... The three-, four-, and five-year overall survival (95 % CI) estimates were 16 % (11 %-21 %), 13 % (8 %-18 %), and 12 % (7 %-17 %), respectively. In IMbrella A, ...