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

Not currently recruiting at 586 trial locations

Overseen By Eric C. McGary

Age: 18+

Sex: Any

Trial Phase: Phase 3

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 All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of two drugs, ramucirumab and pembrolizumab, is more effective than standard chemotherapy for treating stage IV or recurrent non-small cell lung cancer. Ramucirumab may prevent tumors from growing new blood vessels, while pembrolizumab could help the immune system attack cancer cells. Participants with non-small cell lung cancer that has progressed after treatment, including those who have tried anti-PD-1 or PD-L1 therapies, may be suitable for this study. The research aims to determine if the drug combination is more effective than typical chemotherapy treatments. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

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

Research has shown that the combination of ramucirumab and pembrolizumab is generally well-tolerated by people with advanced non-small cell lung cancer. In earlier studies, patients who took this combination experienced some side effects, but they were mostly manageable. Common side effects included fatigue, high blood pressure, and changes in liver function tests, similar to those from other cancer treatments.

In these studies, the combination was compared to regular chemotherapy and did not show more severe side effects than chemotherapy. This suggests that the treatment's safety is comparable to other treatments already used for this type of cancer.

Since this treatment is being tested in a later phase trial, earlier stages have already provided some confidence in its safety. The combination has undergone several rounds of testing to check for serious safety concerns before reaching this point. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for non-small cell lung cancer?

Researchers are excited about the combination of ramucirumab and pembrolizumab for non-small cell lung cancer because it represents a fresh approach compared to traditional chemotherapy options. Unlike chemotherapy, which generally attacks rapidly dividing cells, ramucirumab is an anti-angiogenic drug that works by blocking the blood supply to tumors, effectively starving them. Pembrolizumab, on the other hand, is an immunotherapy that boosts the body's own immune system to recognize and attack cancer cells. This dual-action strategy not only targets the cancer more precisely but may also lead to fewer side effects and improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will compare the combination of ramucirumab and pembrolizumab with standard chemotherapy for treating advanced non-small cell lung cancer (NSCLC). Research has shown that this combination might be promising. Specifically, a study found that patients receiving ramucirumab and pembrolizumab lived longer than those on standard treatment. Ramucirumab blocks the growth of blood vessels that tumors need, while pembrolizumab helps the immune system attack cancer cells. This combination has improved survival in patients whose cancer worsened after previous immunotherapy. These findings suggest that this treatment could be more effective than standard chemotherapy for advanced NSCLC. ^{3 6 7 8 9}

Who Is on the Research Team?

Karen Reckamp, MD

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Pembrolizumab
• Ramucirumab

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

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+

Published Research Related to This Trial

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]

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]

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, 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, 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]

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]

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]

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]

Citations

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Phase II Randomized Study of Ramucirumab and ... Key Objective · Resistance to immunotherapy develops in most advanced non–small-cell lung cancer (NSCLC) treated with immune checkpoint inhibition (ICI).

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Phase II Randomized Study of Ramucirumab and ... This randomized phase II trial demonstrated significantly improved OS with RP compared with SOC in patients with advanced NSCLC previously treated with ICI and ...

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Drug Combo Improved Survival in NSCLC Patients with advanced non-small cell lung cancer whose cancer had progressed on previous immunotherapy lived significantly longer when treated with a ...

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Study Details | NCT03971474 | Ramucirumab and ... Giving ramucirumab and pembrolizumab together may work better in treating patients with non-small lung cancer compared to standard of care. Detailed Description.

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Lung-MAP nonmatched substudy S1800A. Overall survival from a phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non–small cell lung cancer previously ...

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Phase II Randomized Study of Ramucirumab and ... - PubMed This randomized phase II trial demonstrated significantly improved OS with RP compared with SOC in patients with advanced NSCLC previously ...

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Phase II Randomized Study of Ramucirumab and ... This randomized phase II trial demonstrated significantly improved OS with RP compared with SOC in patients with advanced NSCLC previously treated with ICI and ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39453771/

Efficacy, Safety, and Influence on the Tumor ... This new neoadjuvant combination of pembrolizumab plus ramucirumab was feasible, and anti-VEGF agents may enhance the effects of immune checkpoint inhibitors.

9. ecancer.org ecancer.org/en/news/26559-asco-2025-ramucirumab-and-pembrolizumab-combo-does-not-improve-os-for-previously-treated-advanced-nsclc

ASCO 2025: Ramucirumab and pembrolizumab combo ... “For patients enrolled to Pragmatica-Lung, overall survival appears comparable across arms, so the investigational combination may offer ...