Pembrolizumab Dosing Schedules for Non-Small Cell Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must be taking: Pembrolizumab

Must not be taking: High-dose corticosteroids

Disqualifiers: Active infections, Brain metastasis, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two dosing schedules of pembrolizumab, an immunotherapy drug, for treating non-small cell lung cancer. The researchers aim to determine if a 12-week dosing schedule can control the cancer as effectively as the standard 3-week schedule, potentially reducing the number of treatments and associated costs. Individuals who have received pembrolizumab for at least 6 months without disease progression might be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on high-dose corticosteroids, you may need to stop or adjust them, as only low-dose prednisone is allowed for certain conditions.

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

Research shows that pembrolizumab is generally well-tolerated. Studies have found common side effects include fatigue, cough, and skin rash, with most being mild or moderate. Serious side effects, such as lung or liver inflammation, can occur but are less common.

The FDA has already approved pembrolizumab for treating certain cancers, indicating it is safe for these uses. The current study examines administering the treatment every 12 weeks instead of every 3 weeks. This less frequent dosing aims to maintain effectiveness while potentially reducing side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for non-small cell lung cancer?

Researchers are excited about pembrolizumab for non-small cell lung cancer because of its unique dosing schedules being tested. Unlike standard treatments that often require frequent administration, pembrolizumab is being explored in two different regimens: one where it's given every three weeks, and another more novel approach where it's administered every twelve weeks. This extended dosing schedule could potentially reduce hospital visits and improve the quality of life for patients. Additionally, pembrolizumab works by blocking the PD-1 pathway, a mechanism that helps the immune system better recognize and attack cancer cells, offering a promising alternative to traditional chemotherapy.

What evidence suggests that pembrolizumab dosing schedules could be effective for non-small cell lung cancer?

Research has shown that pembrolizumab effectively treats non-small cell lung cancer (NSCLC). Studies have found that it helps patients live longer and keeps the cancer under control for a longer time. Specifically, data from the KEYNOTE trials indicated that pembrolizumab can significantly extend life compared to traditional treatments like chemotherapy. In this trial, participants will receive pembrolizumab in different dosing schedules: one group will receive 200mg every 3 weeks, while another group will receive 200mg every 12 weeks. These findings suggest that pembrolizumab is a promising option for managing NSCLC, offering both effectiveness and potential convenience with flexible dosing schedules. ^{6 7 8 9 10}

Who Is on the Research Team?

Grace Dy, MD

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung cancer who can be treated with pembrolizumab, have stable organ function, and an ECOG performance status of <=2. They must have responded to at least 6 months of pembrolizumab treatment without disease progression. Pregnant women or those on high-dose steroids for brain metastases are excluded.

Inclusion Criteria

I can perform daily activities with minimal assistance.

My kidney function, measured by creatinine or GFR, is within the normal range.

My cancer responded to treatment before, with no major growth or new issues outside the brain.

Exclusion Criteria

I haven't had cancer treatment, except for pembrolizumab, in the last 6 months.

I have brain metastasis but haven't been treated with steroids and it's stable after radiation.

I have used high-dose steroids recently for brain metastases or haven't recovered from their side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab IV over 30 minutes every 3 weeks or every 12 weeks for up to 24 months

24 months

Every 3 weeks or every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

12 months

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study compares the effectiveness of administering pembrolizumab every 12 weeks versus every 3 weeks in patients with non-small cell lung cancer. The goal is to see if less frequent dosing maintains similar disease control while reducing treatment frequency and costs.

How Is the Trial Designed?

Group I: Arm II (200mg pembrolizumab 12 weeks) Experimental Treatment 1 Intervention

Patients receive 200mg pembrolizumab IV over 30 minutes every 12 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (200mg pembrolizumab 3 weeks) Active Control 1 Intervention

Patients receive 200mg pembrolizumab IV over 30 minutes every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Personalized dosing of pembrolizumab at 2 mg/kg could save approximately $825 million annually in the United States compared to the fixed dosing of 200 mg every three weeks, without negatively affecting treatment outcomes.

The study analyzed the economic impact of dosing strategies for pembrolizumab in metastatic non-small cell lung cancer, estimating costs based on patient weight and survival data from the KEYNOTE 024 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phamacoeconomic Analysis of Personalized Dosing vs Fixed Dosing of Pembrolizumab in Firstline PD-L1-Positive Non-Small Cell Lung Cancer. Goldstein, DA., Gordon, N., Davidescu, M., 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]

In a study involving 1,453 patients with advanced melanoma and non-small cell lung cancer (NSCLC), pembrolizumab showed no dependency on dosage for overall survival, indicating that varying doses (2 to 10 mg/kg) did not significantly affect patient outcomes.

A strong association was found between the baseline clearance (CL0) of pembrolizumab and overall survival, suggesting that higher clearance rates may indicate more severe disease, rather than affecting the drug's efficacy directly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Exposure-Response Assessments Challenged by Association of Cancer Cachexia and Catabolic Clearance. Turner, DC., Kondic, AG., Anderson, KM., et al.[2019]

Pembrolizumab, an antibody targeting the PD-1 receptor, has shown strong antitumor effects and manageable safety in patients with advanced solid tumors, based on data from multiple studies including patients with melanoma and lung cancer.

The pharmacokinetic analysis indicates that the standard dose of 2 mg/kg every 3 weeks is effective across various patient subpopulations, with minimal need for dose adjustments based on factors like sex, tumor type, or prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Model-Based Characterization of the Pharmacokinetics of Pembrolizumab: A Humanized Anti-PD-1 Monoclonal Antibody in Advanced Solid Tumors. Ahamadi, M., Freshwater, T., Prohn, M., et al.[2018]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

The 400 mg dose of pembrolizumab administered every 6 weeks (Q6W) is predicted to have similar drug exposure levels as the 200 mg dose given every 3 weeks (Q3W), based on simulations from a model using data from 2993 subjects across multiple cancer trials.

Safety profiles for the 400 mg Q6W regimen are expected to be comparable to the lower doses, as predicted peak concentrations are significantly lower than the maximum clinical dose of 10 mg/kg given every 2 weeks, suggesting that efficacy and safety will be maintained across different dosing schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Lala, M., Li, TR., de Alwis, DP., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6276906/

Systematic evaluation of pembrolizumab dosing in patients ... KEYNOTE-001 supports pembrolizumab 2 mg/kg every 3 weeks as an appropriate dose for previously treated non-small-cell lung cancer.

3. pharmacytimes.com pharmacytimes.com/view/keynote-trial-data-presented-at-esmo-2025-congress-reiterate-pembrolizumab-s-benefits-in-nsclc

KEYNOTE Trial Data Presented at ESMO 2025 Congress ... Pembrolizumab in KEYNOTE-671 improved 5-year overall and event-free survival in resectable NSCLC compared to chemotherapy-placebo, reducing ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0169500224004847

Real-world overall survival after alternative dosing for ... Alternative pembrolizumab dosing reduced median daily dose per patient by 22%. We reported real-world data including overall survival in NSCLC patients.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02885

Five-Year Outcomes With Pembrolizumab Versus ... With > 5 years of follow-up, first-line pembrolizumab monotherapy was associated with substantially longer OS, durable response, and prolonged ...

6. keytrudahcp.com keytrudahcp.com/dosing/options/

Dosing Schedule for KEYTRUDA® (pembrolizumab) | HCP Choose an appropriate dosing regimen for your patients by selecting an indication below. See full Prescribing Information for preparation and administration ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2016/125514s012lbl.pdf

KEYTRUDA (pembrolizumab - accessdata.fda.gov The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over. 30 minutes every 3 weeks until disease progression or unacceptable ...

8. merck.com merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

keytruda_pi.pdf HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use KEYTRUDA safely and effectively. See full prescribing ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04032418

Study Details | NCT04032418 | Pembrolizumab Every 12 ... Patients receive 200mg pembrolizumab IV over 30 minutes every 12 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7273162/

Association of Extended Dosing Intervals or Delays in ... Based on a modeling/simulation study, the dosing schedule of pembrolizumab at 400 mg every 6 weeks has been approved by the European Commission and the FDA. •.