Immunotherapy for Lung Cancer

(RIVAL Trial)

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Michael D Green

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: VA Office of Research and Development

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study is a multicenter Phase II single arm trial to assess the safety and efficacy of chemotherapy and immunotherapy followed by radiotherapy in patients with unresectable Stage III NSCLC.

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 immunosuppressive therapy or corticosteroids, you may need to stop or adjust them, as these are part of the exclusion criteria.

What data supports the effectiveness of the drug Nivolumab (Opdivo) for lung cancer?

Research shows that Nivolumab (Opdivo) significantly improves overall survival and progression-free survival in patients with advanced squamous non-small cell lung cancer compared to the chemotherapy drug docetaxel. It is also better tolerated, meaning patients experience fewer severe side effects. ^{1 2 3 4 5}

Is Nivolumab (Opdivo) generally safe for humans?

Nivolumab, used in lung cancer treatment, can cause unique side effects due to its impact on the immune system. These side effects may affect the skin, digestive system, hormone-producing glands, kidneys, and lungs, and in rare cases, the heart. Early recognition and management of these side effects are important for patient safety. ^{6 7 8 9 10}

What makes the drug Nivolumab unique for treating lung cancer?

Nivolumab is unique because it is an immune checkpoint inhibitor that helps the body's immune system fight cancer by blocking the PD-1 protein, which can prevent the immune system from attacking cancer cells. It is administered intravenously every two weeks and has shown better overall survival and tolerance compared to traditional chemotherapy in patients with advanced non-small cell lung cancer. ^{1 3 5 11 12}

Eligibility Criteria

This trial is for veterans with Stage III NSCLC that can't be removed by surgery. Participants should meet certain health standards, but specific inclusion and exclusion criteria are not listed.

Inclusion Criteria

My cancer shows PD-L1 expression of 1% or more.

Presence of measurable disease according to RECIST v1.1

My organs are working well.

Exclusion Criteria

Inability to provide informed consent

Presence of significant comorbidities precluding participation in a clinical study as determined by investigator

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy and Immunotherapy

Participants receive Nivolumab (Opdivo) plus platinum-doublet chemotherapy

12 weeks

Radiotherapy

Participants undergo radiotherapy following chemotherapy and immunotherapy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately two years

Treatment Details

Interventions

• Nivolumab (Checkpoint Inhibitor)

Trial Overview The study tests the combination of chemotherapy and immunotherapy (Nivolumab), followed by radiotherapy to treat patients with advanced lung cancer that cannot be surgically removed.

Participant Groups

Group I: Chemoimmunotherapy followed by radiotherapy Experimental Treatment 1 Intervention

Nivolumab (Opdivo) + plus platinum-doublet chemotherapy followed by radiotherapy

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Hunter Holmes McGuire VA Medical Center, Richmond, VA Richmond, VA

VA Ann Arbor Healthcare System, Ann Arbor, MI Ann Arbor, MI

Durham VA Medical Center, Durham, NC Durham, NC

VA Greater Los Angeles Healthcare System, West Los Angeles, CA West Los Angeles, CA

More Trial Locations

Who Is Running the Clinical Trial?

VA Office of Research and Development Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018] Progress in the treatment of patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) has been limited. An improvement in the understanding of tumor immunosurveillance has resulted in the development of the immune checkpoint inhibitors such as nivolumab. Nivolumab (Opdivo(®)), a human immunoglobulin (Ig)G4 anti-programmed death (PD)-1 monoclonal antibody, was the first PD-1 inhibitor approved in the treatment of patients with advanced stage squamous cell NSCLC following platinum-based chemotherapy. CHECKMATE 017, a randomized phase III study of second-line nivolumab versus docetaxel, significantly improved overall survival (OS), progression-free survival (PFS), patient reported outcomes and the safety and tolerability favored patients treated with nivolumab. The ligand (PD-L1) expression did not predict for outcome. In this paper, we review the role of nivolumab in the treatment of NSCLC with particular attention on recent studies, ongoing combination studies, toxicity profile, current and potential predictive biomarkers.

2. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of nivolumab in the treatment of metastatic squamous non-small-cell lung cancer. [2020] Until recently, the prognosis and treatment of patients with advanced-stage squamous cell lung cancers have been limited. An improvement in the understanding of the role of the immune system in tumor immunosurveillance has led to the development of the programmed death-1 (PD-1) immune checkpoint inhibitor nivolumab (Opdivo). Nivolumab is the first PD-1 inhibitor approved for the treatment of advanced-stage squamous cell non-small-cell lung cancer following platinum-based chemotherapy. In the key Phase III trial CHECKMATE 017, a better overall survival and progression-free survival were seen in patients treated with second-line nivolumab compared with docetaxel. Programmed death ligand-1 (PD-L1) expression did not predict for outcome. In addition, nivolumab had better safety and tolerability, and led to better patient reported outcomes. Further research on the role of PD-L1 expression as a predictive biomarker should be performed, and other biomarkers that can predict the efficacy of PD-1/PD-L1 inhibitors should also be pursued. Further studies on the combination treatment are ongoing to determine the optimal role of nivolumab as monotherapy or nivolumab with other agents in non-small-cell lung cancer.

3. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022] Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy. In the pivotal CheckMate 017 trial, intravenous nivolumab 3 mg/kg every 2 weeks was associated with significantly better overall survival and progression-free survival and a significantly higher overall response rate than intravenous docetaxel in the second-line treatment of advanced, squamous NSCLC. Nivolumab was also better tolerated than docetaxel in CheckMate 017, and its adverse event profile (which included immune-mediated adverse events) was manageable. In conclusion, nivolumab represents an important advance in previously-treated, advanced, squamous NSCLC.

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

The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials. [2019] Nivolumab is a programmed cell death 1 (PD-1) receptor inhibitor antibody that enhances immune system antitumor activity. Although it is used for treating advanced non-small-cell lung cancer (NSCLC), its actual efficacy has not been determined. We searched PubMed, the Cochrane Library, Embase, MEDLINE, and Web of Science for related noncomparative clinical studies and randomized controlled trials (RCTs) to assess nivolumab benefit and risk in NSCLC. The main outcomes were objective response rate (ORR), 1-year overall survival rate (1-yOS rate), and progression-free survival rate at 24 weeks (PFS at 24 weeks rate), any-grade adverse effects rate (any-grade AEs%), and grade 3-4 AE rate (grade 3-4 AEs%). Relative risk (RR) was used to compare ORR in patients with positive and negative programmed cell death ligand 1 (PD-L1) expression. Random-effects models were used to determine pooled effect size and two-sided 95% confidence intervals (95% CI). We included 20 studies (17 noncomparative open-label cohort studies, three RCTs) involving 3404 patients in our meta-analysis. The modified nivolumab ORR was 18% (95% CI: 15-20%), the 1-yOS rate was 45% (95% CI: 40-50%), PFS at 24 weeks rate was 42% (95% CI: 37-48%), any-grade AEs% was 61% (95% CI: 50-73%), and grade 3-4 AEs% was 12% (95% CI: 9-16%). PD-L1 expression was related with the nivolumab ORR. Nivolumab potentially causes ongoing response, long-term PFS, and reduced treatment-related AEs. PD-L1 expression predicts the outcome of nivolumab immunotherapy. More high-quality and well-designed RCTs with large sample sizes are warranted to prove our findings.

5. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018] The programmed death (PD)-1 immune checkpoint inhibitor nivolumab (Opdivo(®)) is approved in the USA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have progression on or after platinum-based chemotherapy and in the EU for the treatment of adults with locally advanced or metastatic NSCLC after prior chemotherapy. In previously-treated patients with advanced nonsquamous NSCLC, overall survival was significantly prolonged and the overall response rate was significantly higher in patients who received intravenous nivolumab 3 mg/kg every 2 weeks versus intravenous docetaxel in the pivotal CheckMate 057 trial. Progression-free survival did not significantly differ between patients receiving nivolumab and those receiving docetaxel. Intravenous nivolumab had a manageable adverse event profile (including immune-mediated adverse events) and was better tolerated than docetaxel in the CheckMate 057 trial. Thus, nivolumab is an important new option for use in previously-treated patients with advanced nonsquamous NSCLC.

6. Greece pubmed.ncbi.nlm.nih.gov

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer. [2023] The aim of this study was to investigate possible association between adverse events of nivolumab therapy and the effectiveness of treatment in patients with non-small cell lung cancer (NSCLC). Focusing on serious adverse events (i.e., those of grade ≥3), we evaluated overall survival (OS), progression-free survival (PFS), as well as objective response rate (ORR) to treatment.

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

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. [2018] Monoclonal antibodies targeting programmed cell death protein-1 (PD-1) represent a new treatment paradigm in non-small cell lung cancer. Three phase III trials have demonstrated a survival benefit and improved tolerability of nivolumab and pembrolizumab when compared with standard second-line chemotherapy. Nevertheless, the adverse events associated with PD-1 inhibitors are unique; early recognition and treatment are essential. This review summarizes the required monitoring and appropriate management of immune-related adverse events in lung cancer patients receiving these agents.

8. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. [2021] Significant improvement in survival outcome with the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has been shown in advanced non-small cell lung cancer (NSCLC) patients compared with chemotherapy. However, the full spectrum of toxic events of PD-1/PD-L1 inhibitors was not well characterized. We conducted a comprehensive meta-analysis to state the safety profile of PD-1/PD-L1 inhibitors in NSCLC, and identify the exact incidence and relative risk (RR) of both summary and detailed AEs.

9. Ireland pubmed.ncbi.nlm.nih.gov

Drug-induced myocarditis after nivolumab treatment in a patient with PDL1- negative squamous cell carcinoma of the lung. [2022] Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response.

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

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022] Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or

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

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021] Frontline treatment with nivolumab (Opdivo) plus ipilimumab (Yervoy) induced durable and long-term efficacy, compared with chemotherapy, in patients with advanced non-small cell lung cancer (NSCLC) and tumor PD-L1 expression greater than 1% or less than 1%, according to updated results from part 1 of the phase 3 CheckMate 227 (NCT02477826)trial presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.

12. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023] Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer.