Pembrolizumab Dosing Schedules for Non-Small Cell Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

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

9 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well pembrolizumab given every 12 weeks works compared to every 3 weeks in treating patients with non-small cell lung cancer. 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 every 12 weeks may provide similar disease control with fewer treatments for patients with non-small cell lung cancer when compared to every 3 weeks. Demonstrating that 12 week dosing is as effective as 3 week dosing may also have a significant impact when considering the cost required for these medications.

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.

What data supports the effectiveness of the drug pembrolizumab for non-small cell lung cancer?

Pembrolizumab has shown clinical activity in various solid tumors, including non-small cell lung cancer, and is approved for second-line treatment in PD-L1-positive cases. It has demonstrated robust antitumor activity and manageable safety in patients with advanced solid tumors, supporting its use in non-small cell lung cancer. ^{1 2 3 4 5}

Is pembrolizumab safe for humans?

Pembrolizumab has been studied in various conditions, including melanoma and non-small cell lung cancer. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects can include lung inflammation, liver inflammation, and thyroid issues. Despite these risks, the benefits of pembrolizumab in treating life-threatening conditions have been considered to outweigh the potential side effects. ^{1 2 3 4 6}

How is pembrolizumab different from other drugs for non-small cell lung cancer?

Pembrolizumab is unique because it can be administered in two different dosing schedules: a standard 200 mg every 3 weeks or an alternative 400 mg every 6 weeks, offering flexibility in treatment frequency for patients with non-small cell lung cancer. ^{1 7 8 9 10}

Research Team

Grace Dy, MD

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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, 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]

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]

References

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

Pembrolizumab Exposure-Response Assessments Challenged by Association of Cancer Cachexia and Catabolic Clearance. [2019]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

Model-Based Characterization of the Pharmacokinetics of Pembrolizumab: A Humanized Anti-PD-1 Monoclonal Antibody in Advanced Solid Tumors. [2018]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Alternate Pembrolizumab Dosing Interval in Advanced NSCLC with PD-L1 TPS ≥ 50%: 3 Weekly Compared to 6 Weekly Dosing. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. [2021]

9. United States 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. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of individualized pembrolizumab administration based on pharmacokinetic in advanced non-small cell lung cancer: A prospective exploratory clinical trial. [2023]