Ramucirumab + Pembrolizumab vs Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 562 trial locations

Overseen By Eric C. McGary

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Southwest Oncology Group

Must be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: More than one anti-PD-1/PD-L1

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of the combination of ramucirumab and pembrolizumab versus standard of care chemotherapy for the treatment of non-small cell lung cancer that is stage IV or that has come back after a period of improvement (recurrent). Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. 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. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out if giving ramucirumab with pembrolizumab is more effective at treating patients with stage IV or recurrent non-small cell lung cancer than standard chemotherapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug combination of Ramucirumab and Pembrolizumab for non-small cell lung cancer?

Research shows that Pembrolizumab, when combined with chemotherapy, is effective in treating advanced non-small cell lung cancer, improving survival rates and reducing disease progression. Additionally, Pembrolizumab alone has been shown to improve survival in patients with high PD-L1 expression, suggesting its potential effectiveness in combination with other treatments like Ramucirumab. ^{1 2 3 4 5}

Is the combination of Ramucirumab and Pembrolizumab safe for humans?

Pembrolizumab (Keytruda) has been used in various cancer treatments and is generally considered less toxic than traditional chemotherapy, but it can cause side effects like pneumonitis (lung inflammation), fatigue, and nausea. Immune-related side effects such as colitis (inflammation of the colon), hepatitis (liver inflammation), and thyroid disorders have also been reported. While these side effects can be serious, the benefits of treatment often outweigh the risks for life-threatening conditions. ^{1 6 7 8 9}

How is the drug combination of Ramucirumab and Pembrolizumab different from other treatments for non-small cell lung cancer?

This treatment combines Ramucirumab, which targets blood vessels to stop tumor growth, with Pembrolizumab, an immunotherapy that helps the immune system attack cancer cells, offering a unique approach compared to traditional chemotherapy alone. ^{1 3 9 10 11}

Research Team

Karen Reckamp, MD

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with stage IV or recurrent non-small cell lung cancer who've seen their disease progress after anti-PD-1/PD-L1 therapy and platinum-based chemotherapy. They should have had a positive response to previous immunotherapy, be in fair health (Zubrod status 0-2), and able to receive the study drugs safely. Those with certain mutations must have tried FDA-approved targeted therapies.

Inclusion Criteria

I had a positive response to previous immunotherapy for my advanced or recurrent cancer.

My cancer worsened within a year after starting anti-PD-1 or PD-L1 therapy.

My cancer worsened more than 84 days after starting my last anti-PD-1 or PD-L1 therapy.

Exclusion Criteria

I have not had more than one type of immunotherapy for my advanced or recurrent cancer.

Participants must not be receiving or planning to receive another investigational therapy during study participation

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard of care chemotherapy or a combination of ramucirumab and pembrolizumab intravenously

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Chemotherapy (Chemotherapy)
• Pembrolizumab (Monoclonal Antibodies)
• Ramucirumab (Monoclonal Antibodies)

Trial Overview The Pragmatica-Lung Study is testing if combining ramucirumab (a drug that may stop blood vessel growth in tumors) with pembrolizumab (an immune system booster) works better than standard chemotherapy alone for advanced or returning non-small cell lung cancer.

Participant Groups

Group I: ARM B (ramucirumab, pembrolizumab) Experimental Treatment 2 Interventions

Patients receive ramucirumab IV and pembrolizumab IV on study.

Group II: ARM A (standard of care chemotherapy) Active Control 1 Intervention

Patients receive chemotherapy per standard of care on study.

Chemotherapy is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

This trial aims to compare the effectiveness of pembrolizumab combined with chemotherapy versus pembrolizumab alone in patients with advanced non-small-cell lung cancer who have high PD-L1 expression (≥50%).

The study expects that the combination treatment will lead to a lower risk of early disease progression and a higher objective tumor response, providing insights into long-term benefits for patients not eligible for other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression ≥50. Descourt, R., Chouaid, C., Pérol, M., et al.[2021]

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]

In a systematic review and network meta-analysis of first-line treatments for metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC), the combination of pembrolizumab, pemetrexed, and platinum showed a statistically significant improvement in overall survival compared to various other regimens, with hazard ratios ranging from 0.42 to 0.62.

This combination therapy had a 95.6% probability of being the most effective treatment option for overall survival in patients without known targetable mutations, indicating its strong potential as a first-line treatment for this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. Frederickson, AM., Arndorfer, S., Zhang, I., et al.[2022]

Pembrolizumab, an immunotherapy for advanced non-small-cell lung cancer (NSCLC), significantly improves progression-free and overall survival compared to traditional chemotherapy, with fewer side effects, particularly in patients with high PD-L1 expression (≥50%).

In combination with pemetrexed and carboplatin, pembrolizumab also enhances treatment effectiveness and maintains manageable toxicity, leading to a shift in first-line treatment strategies for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. Reck, M.[2018]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

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]

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]

Atezolizumab, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. Isla, D., Sánchez, A., Casal, J., et al.[2023]

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]

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. England pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression ≥50. [2021]

3. 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]

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

Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. [2022]

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

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. [2018]

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

New Approved Use for Keytruda. [2022]

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

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

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

10. Switzerland pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. [2023]

11. 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]