Pembrolizumab for Small Cell Lung Cancer

Overseen By Vanderbilt-Ingram Services for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt-Ingram Cancer Center

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 34

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well pembrolizumab after standard treatment with radiation plus the following chemotherapy drugs: cisplatin or carboplatin, plus etoposide works in treating patients with limited stage small cell lung cancer (LS-SCLC). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab after standard treatment with radiation plus chemotherapy may increase the ability of the immune system to fight LS-SCLC.

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

The trial does not specify if you need to stop taking your current medications. However, if you are on hepatitis B or HIV medications, you should continue them as per the trial guidelines. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Pembrolizumab for Small Cell Lung Cancer?

Research shows that combining radiation therapy and immunotherapy, like pembrolizumab, can improve survival in patients with extensive-stage small cell lung cancer. Additionally, similar treatments using atezolizumab, another immunotherapy drug, with chemotherapy have shown improved outcomes, suggesting potential benefits of pembrolizumab in combination with other therapies. ^{1 2 3 4 5}

Is pembrolizumab safe for humans when used with radiation therapy for small cell lung cancer?

A study combining pembrolizumab with radiation therapy for small cell lung cancer found it to be safe, although the combination has been understudied. Other studies with similar drugs and treatments have shown some side effects like low blood cell counts and esophagitis (inflammation of the esophagus), but they were generally well tolerated. ^{2 3 6 7 8}

How is the treatment with pembrolizumab, carboplatin, etoposide, cisplatin, and radiation therapy unique for small cell lung cancer?

This treatment is unique because it combines pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with chemotherapy and radiation therapy, which are standard treatments for small cell lung cancer. The combination aims to enhance the overall effectiveness by using different methods to target the cancer. ^{3 9 10 11 12}

Research Team

Ryan Whitaker, MD, PhD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Eligibility Criteria

Adults with small cell lung cancer who have completed chemoradiation or surgery followed by chemotherapy can join this trial. They must have a stable immune system, no active infections, and not be pregnant or breastfeeding. Participants should not have other cancers needing treatment, severe allergies to pembrolizumab, or recent vaccinations.

Inclusion Criteria

My small cell lung cancer is in stage I-III and has not spread extensively.

I am 18 or older with a confirmed diagnosis of small cell lung cancer or high-grade neuroendocrine carcinoma.

My hemoglobin level is at least 9.0 g/dL or 5.6 mmol/L, tested within the last 10 days.

Exclusion Criteria

I had radiotherapy over 2 weeks ago, have no ongoing side effects needing steroids, and didn't have lung inflammation from it.

I have not received a live vaccine within the last 30 days.

I am not on high-dose steroids or other drugs that weaken my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Radiation and Chemotherapy

Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles

12 weeks

4 visits (in-person)

Adjuvant Pembrolizumab Treatment

Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity

52 weeks

17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 12 weeks

Treatment Details

Interventions

• Carboplatin, Etoposide, Cisplatin
• Pembrolizumab
• Radiation Therapy

Trial Overview The trial is testing if the drug pembrolizumab improves outcomes when given after standard treatments for limited stage small cell lung cancer. Pembrolizumab is an immunotherapy that may help the body fight cancer more effectively.

Participant Groups

Group I: Treatment (pembrolizumab) Experimental Treatment 9 Interventions

Patients undergo radiation therapy and receive cisplatin or carboplatin on day 1 of each cycle and etoposide on days 1-3 for 4 cycles. Patients then receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan during screening. Patients also undergo MRI throughout the trial as well as CT. Additionally, patients undergo blood sample collection throughout the trial.

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

Merck Sharp & Dohme LLC

Industry 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

In a study of 47 patients with limited disease small-cell lung carcinoma, the combination of carboplatin and etoposide followed by thoracic radiotherapy resulted in a 73% overall response rate, but the median survival time was only 13.7 months, indicating limited long-term efficacy.

The treatment was associated with significant adverse effects, including grade 3-4 neutropenia in 46% of patients and febrile neutropenia in 14%, highlighting safety concerns despite the initial response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited disease small-cell lung cancer: unsatisfactory results. Yilmaz, U., Anar, C., Korkmaz, E., et al.[2022]

In a phase III trial involving 200 patients with stage III non-small cell lung cancer, the chemotherapy regimen of etoposide and cisplatin (EP) showed a significantly higher 3-year overall survival rate compared to carboplatin and paclitaxel (PC), with a difference of 15% (P = 0.024).

While EP demonstrated better overall survival, it was associated with a higher incidence of severe esophagitis (20% vs. 6.3% for PC), whereas PC had a higher rate of radiation pneumonitis (33.3% vs. 18.9% for EP), indicating a trade-off in safety profiles between the two regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Liang, J., Bi, N., Wu, S., et al.[2020]

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 study of 90 patients with limited stage small cell lung cancer, concurrent radiotherapy combined with carboplatin and etoposide significantly improved median survival time to 26 months compared to 19 months for those receiving sequential treatment.

The 5-year survival rate was also better in the concurrent treatment group at 27%, versus 16% in the sequential group, indicating that concurrent treatment may be a more effective approach for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer]. Qiao, TK., Zhou, DA., Xin, L., et al.[2016]

The TREASURE trial is a phase II clinical study involving 104 patients with extensive disease small cell lung cancer (SCLC) to evaluate the effectiveness of adding thoracic radiotherapy (TRT) to atezolizumab maintenance therapy after initial chemo-immunotherapy, with overall survival as the primary endpoint.

This trial aims to enhance treatment outcomes by exploring the synergistic effects of combining immunotherapy with radiotherapy, while also assessing safety and collecting biomarker samples for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial. Bozorgmehr, F., Christopoulos, P., Chung, I., et al.[2022]

The pilot study involving 26 patients with poor-risk Stage III non-small-cell lung carcinoma (NSCLC) showed that the combination of carboplatin, etoposide, and thoracic radiation was well tolerated, with 87% of patients completing the planned radiation treatment.

The treatment resulted in an impressive overall response rate of 87%, with 17% achieving a complete response and a median survival of 12 months, indicating promising efficacy for this regimen in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent carboplatin, etoposide and thoracic radiation for poor-risk stage III non-small-cell lung carcinoma: a pilot study. Lau, DH., Ryu, JK., Gandara, DR., et al.[2019]

In a meta-analysis of 535 patients with extensive small-cell lung cancer, those treated with irinotecan/cisplatin (IP) experienced significantly less severe blood-related side effects, such as grade 3/4 leukopenia, anemia, and thrombocytopenia, compared to those treated with etoposide/cisplatin (EP).

However, patients receiving IP reported higher rates of severe vomiting/nausea and diarrhea, indicating a trade-off in side effects between the two treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of irinotecan/cisplatin versus etoposide/cisplatin for patients with extensive-stage small-cell lung cancer: a metaanalysis. Jiang, L., Yang, KH., Mi, DH., et al.[2018]

In a phase I/II study involving 24 patients with poor-risk stage III non-small cell lung cancer (NSCLC), carboplatin-based chemoradiotherapy was found to be well tolerated, with 96% of patients completing the chemotherapy and 87% completing the planned chest irradiation.

The treatment resulted in an overall response rate of 87%, with 17% achieving a complete response and a median survival of 12 months, indicating promising efficacy for patients who are ineligible for cisplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy for poor-risk stage III non-small cell lung cancer. Lau, DH., Ryu, JK., Gandara, DR.[2013]

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 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, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

References

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

Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited disease small-cell lung cancer: unsatisfactory results. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. [2020]

3. 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]

4. China pubmed.ncbi.nlm.nih.gov

[Concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer]. [2016]

5. England pubmed.ncbi.nlm.nih.gov

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial. [2022]

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

Concurrent carboplatin, etoposide and thoracic radiation for poor-risk stage III non-small-cell lung carcinoma: a pilot study. [2019]

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

Safety of irinotecan/cisplatin versus etoposide/cisplatin for patients with extensive-stage small-cell lung cancer: a metaanalysis. [2018]

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

Chemoradiotherapy for poor-risk stage III non-small cell lung cancer. [2013]

9. 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]

10. 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]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023]