Nivolumab + Ramucirumab for Non-Small Cell Lung Cancer

Recruiting at 1 trial location

Overseen By Hossein Borghaei, DO

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must not be taking: Immunomodulatory agents, Ramucirumab, Antiplatelet therapy

Disqualifiers: Uncontrolled hypertension, Active autoimmune disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two drugs, nivolumab (an immunotherapy drug) and ramucirumab (a targeted therapy drug), in controlling non-small cell lung cancer that has recurred or is difficult to treat after initial therapy. The study examines how well these drugs control the disease in patients who have already received other immune-based or chemotherapy treatments. Suitable candidates for this trial have advanced non-small cell lung cancer, have undergone previous treatment, and have a measurable tumor. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 2 weeks before starting the study. However, if you are on full-dose anticoagulation, you must be on a stable dose for at least 14 days. Please discuss with your doctor to understand how this applies to your specific medications.

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

Previous studies have shown that nivolumab helps treat several types of cancer, including non-small cell lung cancer (NSCLC). The FDA has approved it for use when other treatments are no longer effective. While generally safe, some patients have reported side effects such as tiredness, skin rash, and shortness of breath.

The FDA has also approved ramucirumab for use with docetaxel in treating advanced NSCLC. It is usually well-tolerated, though some patients may experience side effects like high blood pressure and diarrhea.

Since both drugs are approved for treating NSCLC in different combinations, their safety in humans is fairly well known. However, the specific safety of their combination in this trial is still under study. Early results suggest that most side effects can be managed, but patients should monitor their condition and report any concerns to their healthcare team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab and Ramucirumab for non-small cell lung cancer because it offers a novel approach by harnessing the body's immune system. Nivolumab is an immunotherapy drug that works by blocking a protein called PD-1, which helps the immune system identify and attack cancer cells more effectively. Ramucirumab, on the other hand, is a monoclonal antibody that targets VEGFR-2, a receptor involved in the formation of blood vessels that supply tumors. Combining these two treatments could potentially boost the effectiveness of the immune response while simultaneously cutting off the tumor's blood supply, offering a dual attack that is different from standard chemotherapy and radiation therapies.

What evidence suggests that Nivolumab + Ramucirumab could be effective for non-small cell lung cancer?

Research has shown that nivolumab effectively treats non-small cell lung cancer (NSCLC) and has helped many patients unresponsive to other treatments. Studies also indicate that ramucirumab, when combined with another drug, has improved survival rates in NSCLC patients. In this trial, participants will receive a combination of nivolumab and ramucirumab, which might lead to better treatment results, as seen with similar drug combinations. This suggests that using both drugs together could control the disease more effectively than other treatments. ^{4 6 7 8 9}

Who Is on the Research Team?

Hossein Borghaei

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with advanced non-small cell lung cancer that's come back or spread, who've tried one treatment already. They need normal organ/marrow function and no major health issues like serious infections or heart problems. Women of childbearing age must test negative for pregnancy and agree to contraception, as should men with partners who can get pregnant.

Inclusion Criteria

I am older than 18 years.

I have a recent biopsy after my last treatment showed my cancer progressed.

I agree to use contraception since my partner can become pregnant.

Exclusion Criteria

I had cancer before, but it's been in complete remission for over 2 years and I don't need treatment now.

I am still recovering from my last cancer treatment.

I am not currently taking any experimental drugs or immune system modifiers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab and ramucirumab combination therapy to investigate the synergistic effect on NSCLC

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Overall survival and progression-free survival are assessed

60 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Ramucirumab

Trial Overview The trial is testing a combination of two drugs, Nivolumab plus Ramucirumab, in patients whose lung cancer has returned or spread. It's open to those previously treated with immunotherapy regardless of PD-L1 levels. The main goal is to see how well the disease is controlled with this drug combo.

How Is the Trial Designed?

Group I: Patients with prior IO therapy Experimental Treatment 2 Interventions

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

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

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a phase I/II study involving 43 patients with advanced gastric cancer, the combination of nivolumab, paclitaxel, and ramucirumab showed promising antitumor activity, with an overall response rate of 37.2% and a 6-month progression-free survival rate of 46.5%.

The treatment was generally manageable in terms of safety, with 90.7% of patients experiencing treatment-related adverse events, but only two patients had dose-limiting toxicities, indicating that the combination therapy can be tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase I/II Study of Nivolumab Combined with Paclitaxel Plus Ramucirumab as Second-line Treatment in Patients with Advanced Gastric Cancer. Nakajima, TE., Kadowaki, S., Minashi, K., et al.[2023]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

In a study of 53 patients with metastatic renal cell carcinoma treated with nivolumab, those who experienced immune-related adverse events (irAEs) had significantly better overall survival compared to those without irAEs, indicating a potential link between irAEs and treatment efficacy.

The study found that a lower platelet-to-lymphocyte ratio before treatment was a risk factor associated with the development of irAEs, suggesting that this ratio could be a useful predictor for monitoring patient responses to nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma. Kobayashi, K., Iikura, Y., Hiraide, M., et al.[2021]

The combination of ramucirumab and durvalumab was found to have manageable safety, with grade ≥3 treatment-related adverse events occurring in 32.1% of NSCLC, 37.9% of gastric/GEJ, and 42.9% of HCC patients, indicating that while there are risks, they are within acceptable limits for further study.

The treatment showed preliminary efficacy with an objective response rate of 11% for NSCLC and HCC, and 21% for gastric/GEJ, with better outcomes observed in patients with high PD-L1 expression, suggesting that this combination may be particularly beneficial for certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab and durvalumab for previously treated, advanced non-small-cell lung cancer, gastric/gastro-oesophageal junction adenocarcinoma, or hepatocellular carcinoma: An open-label, phase Ia/b study (JVDJ). Bang, YJ., Golan, T., Dahan, L., et al.[2023]

Ramucirumab is a fully human monoclonal antibody that targets and inhibits VEGFR-2, which plays a key role in cancer growth and progression.

It has received FDA approval as a monotherapy for advanced gastric cancer or gastro-oesophageal junction adenocarcinoma in patients who have not responded to previous chemotherapy, marking it as the first treatment approved for this specific condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab: first global approval. Poole, RM., Vaidya, A.[2023]

Ramucirumab, an anti-VEGFR2 agent, has been shown to improve progression-free and overall survival in patients with Non-Small Cell Lung Cancer (NSCLC) when combined with docetaxel, particularly benefiting those with more aggressive tumors.

While treatment with ramucirumab is generally tolerable, it carries risks of severe adverse effects such as neutropenia, febrile neutropenia, hypertension, and potential bleeding, highlighting the need for careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab in the treatment of non-small cell lung cancer. Arrieta, O., Zatarain-Barrón, ZL., Cardona, AF., et al.[2023]

In a study of 35 patients with advanced non-small-cell lung cancer treated with nivolumab, 34.3% experienced immune-related endocrine adverse events (irAEs), primarily thyroid dysfunction, with hyperthyroidism occurring in 22.9% and hypothyroidism in 8.6%.

Despite the occurrence of these endocrine irAEs, which were mostly mild to moderate in severity, patients with these side effects had a longer progression-free survival, although the study did not find a direct link between irAEs and improved cancer prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab? Chmielewska, I., Dudzińska, M., Szczyrek, M., et al.[2021]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

In a phase 2 trial involving 34 patients with unresectable mesothelioma, the combination of ramucirumab and nivolumab achieved an objective response rate (ORR) of 22.6%, which is an improvement over the previously reported 11% for nivolumab alone.

The treatment was found to be safe, with no severe toxicities reported, and showed promising progression-free survival (PFS) and overall survival (OS) rates, particularly in patients with nonepithelioid histology, suggesting further research in this subgroup may be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299. Dudek, AZ., Xi, MX., Scilla, KA., et al.[2023]

In a study involving six patients with EGFR-mutated lung adenocarcinoma, the combination of osimertinib and ramucirumab was found to be generally safe, with only one case of dose-limiting toxicity (grade 3 appetite loss) and no other severe adverse events reported.

Five out of six patients showed a partial response to the treatment, with a median progression-free survival of 9.2 months for those with the EGFR T790M mutation, suggesting promising efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. Akamatsu, H., Ozawa, Y., Oyanagi, J., et al.[2023]

Ramucirumab (Cyramza) is a significant advancement in the treatment of gastric cancer, targeting the vascular endothelial growth factor receptor 2 (VEGFR-2) to inhibit tumor blood supply.

Clinical studies have demonstrated that ramucirumab improves overall survival in patients with advanced gastric cancer, making it a crucial option for those with this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab (Cyramza): A Breakthrough Treatment for Gastric Cancer. Singh, AD., Parmar, S.[2020]

In a phase 3 trial involving 1253 patients with stage IV non-small-cell lung cancer, the combination of ramucirumab and docetaxel significantly improved overall survival (10.5 months) compared to docetaxel plus placebo (9.1 months), indicating its efficacy as a second-line treatment.

While treatment with ramucirumab was associated with a higher incidence of certain adverse events, such as neutropenia and fatigue, these side effects were manageable, and the overall safety profile was acceptable, with no significant difference in severe adverse events between the treatment and control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Garon, EB., Ciuleanu, TE., Arrieta, O., et al.[2023]

Citations

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Ramucirumab and S-1 After Nivolumab for Patients With ... Subsequent cytotoxic chemotherapy, especially immediately after nivolumab, has better treatment efficacy than that of regimens without ICI pretreatment.

2. opdivohcp.com opdivohcp.com/efficacy/nsclc

Efficacy Data for Non-Small Cell Lung Cancer (NSCLC) - Opdivo Find OPDIVO® (nivolumab) efficacy information for the treatment of non-small cell lung cancers ... outcome, occurred in <1% of patients unless otherwise specified ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0169500219307287

Real-world effectiveness and safety of nivolumab in ... In previous clinical trials, nivolumab has shown activity in several tumor types, including melanoma, renal cell carcinoma, non-small cell lung cancer (NSCLC), ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT381747

Outcomes in non-small cell lung cancer (NSCLC) patients ... Twenty-seven (84%) patients received a combination of carboplatin, pembrolizumab, and pemetrexed, whereas five (16%) patients received ICI monotherapy (3 ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1247879/full

Clinical outcomes of ramucirumab plus docetaxel in the ... In the REVEL trial, ramucirumab plus docetaxel demonstrated significant improvements in overall survival (OS), progression free survival (PFS), ...

6. opdivohcp.com opdivohcp.com/safety/nsclc

Safety Profile for Non-Small Cell Lung Cancer (NSCLC) View the OPDIVO® (nivolumab) safety profiles for the treatment of metastatic non-small cell lung cancers (mNSCLC). Please see Indications and Important ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4718430/

Ramucirumab for the Treatment of Metastatic Non-Small Cell ... Ramucirumab is approved by the US Food and Drug Administration for use with docetaxel for the treatment of patients with metastatic non-small cell lung cancer

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03527108

NCT03527108 | Nivolumab Plus Ramucirumab in Patients ... Patients must have histologically or cytologically confirmed, refractory or recurrent, advanced non-small cell lung carcinoma regardless of histology. Patients ...

9. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2457390

Benefit-Risk Summary of Nivolumab for Patients With ... The FDA granted nivolumab traditional approval on March 4, 2015, for treatment of metastatic SQ NSCLC with progression during or after platinum-based ...