Pembrolizumab + Chemotherapy for Non-Small Cell Lung Cancer

Overseen By Penny Chipman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must not be taking: Immunosuppressants, Corticosteroids, Anticancer agents, others

Disqualifiers: Immunodeficiency, Pneumonitis, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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: Unknown

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, randomized, single-site, open-label Phase II trial of neoadjuvant pembrolizumab (3 cycles) followed by surgery, versus concomitant neoadjuvant pembrolizumab with platinum doublet chemotherapy (3 cycles) followed by surgery for participants with Stage IA3, IB and IIA non-small-cell lung cancer (NSCLC). Participants will be offered pembrolizumab (6 cycles), and standard of care adjuvant chemotherapy (4 cycles) if applicable.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive drugs, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

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

Pembrolizumab has been shown to significantly improve survival rates in patients with advanced non-small cell lung cancer, especially those with high levels of a protein called PD-L1. Studies have demonstrated that patients receiving pembrolizumab had better outcomes compared to those receiving traditional chemotherapy. ^{1 2 3 4 5}

Is pembrolizumab (Keytruda) safe for humans?

Pembrolizumab (Keytruda) has been used in various clinical trials and is generally considered safe, but it can cause side effects. Common side effects include fatigue, cough, nausea, and rash, while more serious ones can include pneumonitis (lung inflammation) and thyroid disorders. It's important to discuss potential risks with your doctor. ^{1 3 6 7 8}

How is the drug pembrolizumab plus chemotherapy unique for treating non-small cell lung cancer?

Pembrolizumab, when combined with chemotherapy, is unique because it uses the body's immune system to help fight cancer by blocking a pathway (PD-1/PD-L1) that tumors use to hide from immune cells, and it is now a standard first-line treatment for advanced non-small cell lung cancer. ^{1 3 9 10 11}

Research Team

Jonathan Spicer, MD, PhD

Principal Investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Eligibility Criteria

This trial is for adults with early-stage Non-Small Cell Lung Cancer (NSCLC) who haven't been treated before. They must be physically well enough to handle the treatments and surgery, not pregnant or breastfeeding, and willing to use contraception. People can't join if they've had severe reactions to pembrolizumab or chemo drugs, recent radiation therapy, other cancer treatments or trials within 4 weeks, certain health conditions that could affect the trial results, a history of significant lung disease or immune disorders.

Inclusion Criteria

I am a man and agree not to donate sperm and to use birth control or remain abstinent.

My lung cancer is in an early stage and has not been treated yet.

I am not pregnant, not breastfeeding, and either cannot become pregnant or am using birth control.

Exclusion Criteria

My lung cancer is a specific type affecting the upper part of my lung, or is LCNEC or sarcomatoid.

I do not have another cancer that is getting worse or needs treatment in the last 5 years.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pembrolizumab every 3 weeks for 3 cycles, with or without histology-specific chemotherapy

9 weeks

Surgery

Surgical resection of the tumor is performed after neoadjuvant treatment

1 week

Adjuvant Treatment

Participants receive pembrolizumab every 6 weeks for 6 cycles, and may receive adjuvant chemotherapy if indicated

36 weeks

Follow-up

Participants are monitored for safety, effectiveness, and ctDNA resolution after treatment

Up to 3 years

Treatment Details

Interventions

• Pembrolizumab

Trial Overview The study tests neoadjuvant pembrolizumab alone versus pembrolizumab with platinum-based chemotherapy before surgery in NSCLC patients. It's randomized and open-label; some will also get standard adjuvant chemotherapy after surgery depending on their situation.

Participant Groups

Group I: Neoadjuvant pembrolizumab and chemotherapy + adjuvant pembrolizumab +/- adjuvant chemotherapy Experimental Treatment 4 Interventions

Neoadjuvant: Participants receive pembrolizumab \[200 mg, intravenous (IV)\] every 3 weeks for 3 cycles in combination with standard of care histology-specific chemotherapy \[consisting of carboplatin AUC 6 and paclitaxel 200 mg/m2, or carboplatin AUC 5 and paclitaxel 500 mg/m2\] every 3 weeks for 3 cycles. Adjuvant: Participants receive pembrolizumab \[400 mg IV\] every 6 weeks for 6 cycles, and may receive histology-specific adjuvant chemotherapy \[consisting of carboplatin AUC 6 and paclitaxel 200 mg/m2, or carboplatin AUC 5 and paclitaxel 500 mg/m2\] every 3 weeks for 4 cycles, if indicated.

Group II: Neoadjuvant pembrolizumab + adjuvant pembrolizumab +/- adjuvant chemotherapy Experimental Treatment 4 Interventions

Neoadjuvant: Participants receive pembrolizumab \[200 mg, intravenous (IV)\] every 3 weeks for 3 cycles. Adjuvant: Participants receive pembrolizumab \[400 mg IV\] every 6 weeks for 6 cycles, and may receive histology-specific adjuvant chemotherapy \[consisting of carboplatin AUC 6 and paclitaxel 200 mg/m2, or carboplatin AUC 5 and paclitaxel 500 mg/m2\] every 3 weeks for 4 cycles, if indicated.

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?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Findings from Research

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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

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 metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., 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, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

References

1. 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]

2. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

3. England pubmed.ncbi.nlm.nih.gov

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

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

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

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

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

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. [2022]

11. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]