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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether pembrolizumab can help the immune system fight small cell lung cancer after standard treatments like radiation and chemotherapy. Pembrolizumab, a type of immunotherapy, may help the body attack cancer cells and prevent their growth. Individuals diagnosed with limited-stage small cell lung cancer who have already received radiation and chemotherapy but still need more treatment might be suitable for this trial. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

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.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab is generally well-tolerated by patients. In studies involving individuals with lung cancer, this treatment proved to be safe. Some patients experienced side effects, but these were often manageable. Common side effects included tiredness and nausea, similar to those seen with other cancer treatments.

The FDA has already approved pembrolizumab for other types of cancers, such as non-small cell lung cancer, indicating its safety for use in other conditions. However, since this trial involves a different form of lung cancer, monitoring for any new side effects is crucial.

Participants in this trial will be closely monitored by doctors for any side effects. The aim is to detect and address any issues early, ensuring the treatment remains as safe as possible for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it harnesses the power of immunotherapy, a newer approach in cancer treatment, to target small cell lung cancer (SCLC). Unlike traditional chemotherapy treatments like cisplatin and etoposide, which attack cancer cells directly, pembrolizumab works by boosting the body's immune system to recognize and fight cancer cells. Researchers are excited about pembrolizumab because it offers a potentially more targeted and effective way to treat SCLC, with the hope of improving outcomes and reducing some of the harsh side effects associated with conventional chemotherapy.

What evidence suggests that pembrolizumab might be an effective treatment for small cell lung cancer?

Research shows that pembrolizumab, which participants in this trial will receive, may help treat small cell lung cancer (SCLC). Studies have demonstrated lasting improvements for patients using pembrolizumab. Specifically, 94% of patients experienced benefits for at least 6 months, and 63% saw improvements for over a year. Pembrolizumab enhances the immune system's ability to fight cancer cells. This treatment, known as immunotherapy, has also proven effective for other types of lung cancer. These findings suggest that pembrolizumab could be a valuable option for people with limited-stage SCLC. ^{1 3 6 7 8}

Who Is on the Research Team?

Ryan Whitaker, MD, PhD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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 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 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]

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]

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]

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]

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]

Citations

1. 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8636217/

The 5‐year outcomes of the KEYNOTE‐024 trial Pembrolizumab monotherapy could provide meaningful improved patient outcomes over platinum‐based chemotherapy for advanced NSCLC patients with PD‐L1 TPS ≥ 50%.

3. 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.

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. 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 ...

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

NCT02142738 | Study of Pembrolizumab (MK-3475) ... The primary hypothesis of this study is that participants with PD-L1 strong NSCLC will have a longer Progression Free Survival (PFS), as assessed by Response ...

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.