Chemoradiation + Pembrolizumab/Olaparib for Small Cell Lung Cancer

Recruiting at 198 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

672 Participants Needed

Trial Summary

What is the purpose of this trial?

Researchers are looking for new ways to treat Limited-Stage Small Cell Lung Cancer (LS-SCLC), a type of lung cancer that has not spread from the lung to other parts of the body. The purpose of this study is to learn if pembrolizumab and olaparib, when given with chemotherapy and radiation treatment (CRT), can be effective in treating LS-SCLC. The researchers want to know if participants who receive CRT and pembrolizumab, with or without olaparib, have a longer overall survival compared to participants who only receive CRT.

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.

What data supports the effectiveness of the treatment combining chemoradiation, pembrolizumab, and olaparib for small cell lung cancer?

Research shows that pembrolizumab, when used with chemotherapy and radiation, has shown promise in treating small-cell lung cancer by improving progression-free survival, although overall survival benefits were not definitive. Pembrolizumab has been approved for use in certain cases of small-cell lung cancer due to its ability to enhance the immune system's response against tumors. ^{1 2 3 4 5}

Is the combination of chemoradiation and pembrolizumab/olaparib generally safe for humans?

Research has shown that combining pembrolizumab with radiation therapy after chemotherapy is being studied for safety in small cell lung cancer. Additionally, pembrolizumab and olaparib are being evaluated for safety in combination with chemoradiotherapy in lung cancer, suggesting ongoing research into their safety profile. ^{1 2 5 6 7}

What makes the treatment of Chemoradiation + Pembrolizumab/Olaparib for Small Cell Lung Cancer unique?

This treatment is unique because it combines chemoradiation with pembrolizumab, an immunotherapy drug that helps the immune system fight cancer, and olaparib, a drug that targets cancer cell repair mechanisms, offering a novel approach for small cell lung cancer, which has limited treatment options and a high risk of progression. ^{1 2 7 8 9}

Research Team

Medical Director, MD

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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 another cancer besides the one being studied that has needed treatment in the last 5 years.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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]

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]

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]

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]

References

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

Rationale and Design of the Phase 3 KEYLYNK-013 Study of Pembrolizumab With Concurrent Chemoradiotherapy Followed by Pembrolizumab With or Without Olaparib for Limited-Stage Small-Cell Lung Cancer. [2022]

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

Phase I Trial of Pembrolizumab and Radiation Therapy after Induction Chemotherapy for Extensive-Stage Small Cell Lung Cancer. [2023]

3. United States 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. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Evidence to Date: Evaluating Pembrolizumab in the Treatment of Extensive-Stage Small-Cell Lung Cancer. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab and paclitaxel in patients with relapsed or refractory small-cell lung cancer. [2020]

6. United States 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. [2023]

7. United States 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. [2022]

8. United States 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. [2022]

9. China pubmed.ncbi.nlm.nih.gov

[Efficacy of olaparib combined with pembrolizumab in second-line treatment for extensive-stage small cell lung cancer]. [2020]