Chemoradiation + Pembrolizumab/Olaparib for Small Cell Lung Cancer

Not currently recruiting at 248 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Anti-PD-1, PARP inhibitors

Disqualifiers: MDS/AML, Immunodeficiency, Autoimmune, others

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

Compensation: Varies

Number of Visits: 13

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for Limited-Stage Small Cell Lung Cancer (LS-SCLC), a type of lung cancer confined to the lungs. Researchers are testing whether adding pembrolizumab (an immunotherapy drug) and olaparib (a targeted therapy) to standard chemotherapy and radiation can extend survival compared to the usual treatment alone. The trial includes different groups to evaluate the effectiveness of pembrolizumab alone or with olaparib. Individuals with confirmed LS-SCLC, who have not received previous treatment and whose cancer has not spread, might be suitable for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these medications before starting the trial.

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

Research has shown that pembrolizumab is generally well-tolerated by patients. In one study, when combined with chemotherapy, about 19% of certain lung cancer patients survived for five years, suggesting it can be a safe option for many. Known side effects exist, but they are often manageable.

When combined with olaparib, pembrolizumab maintains expected safety levels for each drug individually. Previous studies did not find any unexpected safety issues with this combination. Common side effects include tiredness and nausea, but these are usually mild. Researchers closely monitor these effects during trials to ensure patient safety.

Overall, while pembrolizumab and olaparib continue to be studied, existing evidence supports their safety for many patients in clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for small cell lung cancer because they leverage innovative combinations of immunotherapy and targeted therapy. Unlike the standard chemotherapy regimen, which typically involves etoposide and platinum with radiotherapy, the experimental treatments in this trial add pembrolizumab, an immune checkpoint inhibitor, and olaparib, a PARP inhibitor, to the mix. Pembrolizumab enhances the immune system's ability to detect and destroy cancer cells, while olaparib targets cancer cell DNA repair mechanisms, potentially leading to more effective cancer control. This dual approach aims to improve treatment outcomes and offer new hope for patients with this aggressive cancer type.

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

Research has shown that pembrolizumab effectively treats small cell lung cancer (SCLC), with many patients experiencing long-lasting benefits. One study found that 94% of patients who responded to pembrolizumab experienced benefits lasting 6 months or more. In this trial, some participants will receive pembrolizumab with standard chemotherapy and thoracic radiotherapy. Another group will receive pembrolizumab combined with olaparib, alongside the same standard treatments. Although studies on the combination of pembrolizumab and olaparib did not show better results in slowing the disease or improving survival in non-small cell lung cancer, pembrolizumab remains promising due to its proven effectiveness and safety in treating various lung cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Director, MD

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, treatment-naïve Limited-Stage Small Cell Lung Cancer (LS-SCLC) who have a good performance status and can be treated with radiation. They must not have received any prior treatments for LS-SCLC or have any history of certain diseases like HIV, Hepatitis B/C, or autoimmune disease requiring recent treatment. Participants should not be pregnant, must agree to use contraception, and cannot have participated in another investigational study recently.

Inclusion Criteria

I have been diagnosed with pure Small Cell Lung Cancer.

I am not pregnant and will follow birth control advice during and after the study.

You are expected to live for at least 6 more months.

Exclusion Criteria

I am currently being treated for an infection.

I have a history of HIV, Hepatitis B, or active Hepatitis C.

I have had lung inflammation that needed steroids.

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 standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab or placebo every 3 weeks concurrently with standard thoracic radiotherapy

12 weeks

4 visits (in-person)

Maintenance

Participants receive 9 cycles of pembrolizumab every 6 weeks with or without olaparib for 12 months

12 months

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

82 months

What Are the Treatments Tested in This Trial?

Interventions

• Etoposide
• Olaparib
• Pembrolizumab
• Platinum
• Prophylactic Cranial Irradiation (PCI)
• Standard Thoracic Radiotherapy

Trial Overview The trial tests if adding pembrolizumab (an immunotherapy drug) and olaparib (a PARP inhibitor) to standard chemoradiation therapy improves survival without cancer progression compared to chemoradiation alone. Patients are randomly assigned to receive either the new combination of drugs or a placebo alongside their regular cancer treatment.

How Is the Trial Designed?

Group I: Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BID Experimental Treatment 7 Interventions

Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg Q6W plus olaparib 300 mg BID for 12 months or until specific discontinuation criteria are met.

Group II: Group A - Pembrolizumab 200 mg Experimental Treatment 7 Interventions

Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg every 3 weeks (Q3W) concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg every 6 weeks (Q6W) plus olaparib matching placebo twice daily (BID) for 12 months or until specific discontinuation criteria are met.

Group III: Group C (Pembrolizumab and Olaparib Matching Placebos) Placebo Group 6 Interventions

Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab placebo (saline) Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab placebo (saline) Q6W plus olaparib matching placebo for 12 months or until specific discontinuation criteria are met.

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

Approved in United States as Etoposide for:

• Testicular cancer
• Small cell lung cancer
• Non-Hodgkin lymphoma
• Acute myeloid leukemia

Approved in European Union as Etoposide for:

• Testicular cancer
• Small cell lung cancer
• Non-Hodgkin lymphoma
• Acute myeloid leukemia

Approved in Canada as Etoposide for:

• Testicular cancer
• Small cell lung cancer
• Non-Hodgkin lymphoma
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

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

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

Published Research Related to This Trial

In a phase I trial involving 38 patients with extensive-stage small cell lung cancer, the combination of pembrolizumab and thoracic radiotherapy was found to be safe, with no dose-limiting toxicities observed in the first 35 days of treatment.

The median progression-free survival was 6.1 months and overall survival was 8.4 months, suggesting that while the safety profile is promising, further studies are needed to fully understand the efficacy of this combined treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Pembrolizumab and Radiation Therapy after Induction Chemotherapy for Extensive-Stage Small Cell Lung Cancer. Welsh, JW., Heymach, JV., Chen, D., et al.[2023]

In a phase III study with 453 patients, pembrolizumab combined with etoposide and platinum significantly improved progression-free survival (PFS) compared to placebo plus etoposide and platinum, with a 12-month PFS of 13.6% versus 3.1%.

While pembrolizumab plus EP also prolonged overall survival (OS), the results did not meet the predefined significance threshold; however, the treatment showed a favorable safety profile with no unexpected toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. Rudin, CM., Awad, MM., Navarro, A., et al.[2021]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

In a study of 21 patients with extensive stage-small cell lung cancer, the combination of olaparib and pembrolizumab resulted in a median progression-free survival of 5.93 months, compared to 3.53 months for pembrolizumab alone, indicating improved efficacy.

The combination therapy also showed a higher objective response rate of 45.5% versus 10.0% for pembrolizumab alone, suggesting that olaparib enhances the effectiveness of pembrolizumab in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of olaparib combined with pembrolizumab in second-line treatment for extensive-stage small cell lung cancer]. Wu, ZZ., Zhang, SJ., Hu, Y.[2020]

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., et al.[2022]

The KEYLYNK-012 study is a phase III clinical trial evaluating the effectiveness of pembrolizumab combined with chemoradiotherapy in patients with stage III non-small-cell lung cancer (NSCLC), involving participants aged 18 and older with unresectable disease.

This study aims to determine if the addition of pembrolizumab, with or without olaparib, improves progression-free survival and overall survival compared to standard concurrent chemoradiotherapy, with enrollment ongoing at around 190 sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Phase III KEYLYNK-012 Study of Pembrolizumab and Concurrent Chemoradiotherapy Followed by Pembrolizumab With or Without Olaparib for Stage III Non-Small-Cell Lung Cancer. Jabbour, SK., Cho, BC., Bria, E., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor targeting the PD-1 pathway, has shown significant durability of responses in previously treated patients with extensive-stage small-cell lung cancer (ES-SCLC), leading to its accelerated approval by the FDA for second- or third-line treatment.

In a recent clinical trial, pembrolizumab combined with platinum/etoposide improved progression-free survival in previously untreated ES-SCLC patients, although it did not demonstrate a significant improvement in overall survival compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence to Date: Evaluating Pembrolizumab in the Treatment of Extensive-Stage Small-Cell Lung Cancer. Riano, I., Patel, SR., Liu, SV., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8293071/

Evidence to Date: Evaluating Pembrolizumab in the Treatment ... Prospective trials of pembrolizumab in patients with previously treated SCLC showed significant durability of responses. These results led to ...

2. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.7502

Pembrolizumab (MK-3475) in patients (pts) with extensive- ... Responses are durable, with all responders on treatment for 16+ wks with ongoing response. Conclusions: Pembrolizumab is generally well ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02142738

NCT02142738 | Study of Pembrolizumab (MK-3475) ... This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies.

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-metastatic-small-cell-lung-cancer

FDA approves pembrolizumab for metastatic small cell ... Responses were durable for 6 months or longer in 94%, 12 months or longer in 63%, and 18 months or longer in 56% of the 16 responding patients.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02142738

NCT02142738 | Study of Pembrolizumab (MK-3475) ... This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39952082/

Five-year efficacy and safety of pembrolizumab as first-line ... The real-world 5-year survival rate of NSCLC cases with PD-L1 ≥ 50 % treated with first-line pembrolizumab was comparable to that in a clinical trial.

8. keytruda.com keytruda.com/non-small-cell-lung-cancer/combination-therapy-clinical-trial-results/

Advanced Nonsquamous NSCLC Combination Therapy See results of a clinical trial for a combination therapy for certain patients with advanced nonsquamous non–small cell lung cancer.