Nivolumab for Cancer Post-Surgery

(CheckMate 274 Trial)

Not currently recruiting at 414 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Prior malignancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Nivolumab (Opdivo) to determine if it prevents cancer recurrence after surgery for invasive urothelial cancer, which affects the bladder, ureter, or renal pelvis. The trial compares Nivolumab to a placebo (a substance with no active drug) to evaluate effectiveness. It targets individuals who underwent major surgery to remove their cancer and face a high risk of recurrence. Participants who have not received certain chemotherapy before must be unable or unwilling to take it now. They must show no current signs of cancer and provide a tumor sample for study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids or other immunosuppressive medications at least 14 days before starting the study drug.

Is there any evidence suggesting that Nivolumab is likely to be safe for humans?

Studies have shown that Nivolumab, also known as OPDIVO®, is generally well-tolerated by patients. Previous research identified the most common serious side effects in more than 2% of patients as lung infections, blood clots in the lungs, and difficulty breathing. Although these side effects sound serious, they are uncommon for most people.

One study found that people taking Nivolumab after surgery for bladder or urinary tract cancer had a 30% lower chance of cancer returning compared to those who took a placebo (a treatment with no active ingredients). This demonstrates Nivolumab's effectiveness, though, like any medication, it may come with risks.

Side effects can vary from person to person, and doctors will monitor patients closely to manage any issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nivolumab is unique because it leverages the body's own immune system to fight cancer, which is different from traditional chemotherapy that targets cancer cells directly. Most treatments for cancer after surgery aim to kill remaining cancer cells using chemical agents, but nivolumab is a type of immunotherapy that works by blocking a protein called PD-1. This allows the immune system to better recognize and attack cancer cells. Researchers are excited about nivolumab because it has the potential to offer a more targeted approach with fewer side effects and could improve long-term outcomes for patients.

What evidence suggests that Nivolumab might be an effective treatment for invasive urothelial cancer?

Research has shown that Nivolumab, which participants in this trial may receive, can help reduce the chance of cancer returning after surgery. One study found that individuals who took Nivolumab remained cancer-free for an average of 22 months, compared to about 11 months for those who did not. Another study showed that using Nivolumab after surgery reduced the risk of cancer recurrence by 30%. Additionally, three years after treatment, 63.1% of patients who received Nivolumab showed no signs of cancer, compared to 52.5% of those who didn’t receive it. These findings suggest that Nivolumab may be a promising option for extending the time without cancer after surgery. Participants in this trial will be randomized to receive either Nivolumab or a placebo. ^{4 6 7 8 9}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for patients who've had surgery to remove high-risk invasive urothelial cancer from the bladder, ureter, or renal pelvis. They should be currently free of disease (confirmed by imaging), have not received cisplatin chemotherapy before surgery unless ineligible or refusing further cisplatin treatment.

Inclusion Criteria

I can provide a sample of my tumor for testing.

I had a high-risk bladder, ureter, or kidney cancer.

Must have disease free status as determined by imaging within 4 weeks of dosing

Exclusion Criteria

I haven't taken steroids or immune-weakening drugs in the last 14 days.

Positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

Subjects with active, known or suspected autoimmune disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab or placebo following radical surgery for invasive urothelial cancer

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

53 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Placebo

Trial Overview The study is testing Nivolumab, an immunotherapy drug, against a placebo to see if it's more effective in preventing cancer recurrence after radical surgery. Participants will randomly receive either Nivolumab or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Nivolumab Experimental Treatment 1 Intervention

Nivolumab dose as specified

Group II: Placebo Placebo Group 1 Intervention

Placebo dose as specified

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?

Bristol-Myers Squibb

Lead 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

Ono Pharmaceutical Co. Ltd

Industry Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Published Research Related to This Trial

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Nivolumab, an immunotherapy drug, can cause immune-mediated side effects like colitis, which may occur even after treatment has stopped.

Using higher doses of methylprednisolone led to a quicker resolution of symptoms in patients compared to previous cases, potentially reducing the need for hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and immune-mediated colitis. Walker, H., Brennan, P., Groome, M., et al.[2023]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

In a study of patients with non-small cell lung cancer treated with nivolumab, those who experienced serious adverse events (grade ≥3) had significantly better overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared to those without such events.

The findings suggest that while serious adverse events are typically concerning, they may be associated with a more favorable treatment response in patients receiving nivolumab, indicating a complex relationship between adverse effects and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer. Blazek, J., Hosek, P., Hrabcova, K., et al.[2023]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

Citations

1. opdivohcp.com opdivohcp.com/efficacy/nsclc/77t

See the impact of pCR* in your patients 2,3 - Opdivo View efficacy information for perioperative OPDIVO® (nivolumab) + chemotherapy in resectable non-small cell lung cancer (NSCLC). Please see Indications and ...

2. cancer.gov cancer.gov/news-events/cancer-currents-blog/2023/bladder-cancer-nivolumab-adjuvant-therapy

Nivolumab after Surgery for Bladder Cancer - NCI These results showed that people who received nivolumab had a median disease-free survival of 22 monthsExit Disclaimer, compared with about 11 ...

3. asco.org asco.org/about-asco/press-center/news-releases/adding-nivolumab-chemoradiotherapy-after-surgery-can-decrease-chance-recurrence

Adding Nivolumab to Chemoradiotherapy After Surgery ... In the patients who received nivolumab, 63.1% had no signs of cancer recurrence 3 years after treatment vs. 52.5% of patients who received ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7779284/

Effective Treatment of NSCLC with Surgery After ... At a follow-up of 30 months, 15 of 20 patients were disease-free and alive. The 24m RFS rate was 69% (95% CI: 51–93). ... In terms of safety, this study showed ...

5. opdivo.com opdivo.com/bladder-urinary-tract-cancer/clinical-trial-results/after-surgery-immunotherapy

Clinical trial results for bladder or urinary tract cancer after ... People given OPDIVO had a 30% lower risk of their cancer returning after surgery than those given placebo.

6. opdivohcp.com opdivohcp.com/safety/nsclc/77t

Perioperative OPDIVO® (nivolumab) + Chemo Safety Profile ... The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39264379/

Efficacy and safety of adjuvant nivolumab after radical ... Nine patients had recurrences and one died of cancer. Of the nine patients with recurrences, six relapsed while on adjuvant nivolumab therapy, two relapsed ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0022522323009005

Surgical outcomes after chemotherapy plus nivolumab and ... Surgical resections are feasible and safe, with high rates of R0 after neoadjuvant chemotherapy and nivolumab with or without ipilimumab.

9. nejm.org nejm.org/doi/pdf/10.1056/NEJMoa2502931

Overall Survival with Neoadjuvant Nivolumab plus ... Subsequently, several clinical trials have shown similar improvements in pathological response or survival outcomes with perioperative immu-.