Nivolumab Safety for Cancer

Recruiting at 545 trial locations

Overseen By BMS Study Connect Contact http://www.bmsstudyconnect.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bristol-Myers Squibb

Disqualifiers: No clinical benefit, Adverse events, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Long-term

1500 Participants Needed

Trial Summary

What is the purpose of this trial?

Main Objective of this study is to examine long-term safety of nivolumab monotherapy including combinations and other cancer therapies in various tumor types.

Will I have to stop taking my current medications?

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

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

Research shows that Nivolumab, used for non-small cell lung cancer (NSCLC), improves overall survival and progression-free survival compared to traditional chemotherapy. It has been effective in both squamous and non-squamous types of NSCLC, with a favorable safety profile. ^{1 2 3 4 5}

Is Nivolumab safe for humans?

Nivolumab, also known as Opdivo, is generally considered safe but can cause immune-related side effects, such as inflammation in various organs, and rare but serious blood-related issues. It has been associated with diabetic ketoacidosis (a serious diabetes complication) and other immune reactions, especially when combined with other drugs like ipilimumab. ^{6 7 8 9 10}

How does the drug nivolumab differ from other cancer treatments?

Nivolumab is unique because it is an immune checkpoint inhibitor that targets the PD-1 pathway, helping the immune system recognize and attack cancer cells. Unlike traditional chemotherapy, it is administered intravenously and has a different side effect profile, often being better tolerated. ^{5 11 12 13 14}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for cancer patients who have previously been treated with Nivolumab, either completed the treatment, experienced progression during it, or stopped due to side effects. They can join for long-term safety follow-up but not receive further Nivolumab unless deemed beneficial by the original study criteria.

Inclusion Criteria

I have not completed, progressed on, or stopped nivolumab due to side effects.

I am eligible for nivolumab treatment according to my doctor or the main study.

I have finished or am in the follow-up phase of a previous study.

Exclusion Criteria

Participants in survival follow-up have no exclusion criteria.

Any clinical adverse event (AE), laboratory abnormality, or intercurrent illness which, in the opinion of the Investigator, indicates that participation in the study is not in the best interest of the participant

Participants not receiving clinical benefit as assessed by the Investigator (participant is still eligible for study if entering survival follow-up only)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various experimental cancer therapies including Nivolumab monotherapy and combinations with other drugs

Long-term

Follow-up

Participants are monitored for long-term safety and effectiveness of the treatments

6 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Indefinite

Treatment Details

Interventions

• Nivolumab

Trial Overview The main focus of this rollover study is to monitor the long-term safety of Nivolumab in participants who are currently receiving or have received it as part of an earlier 'Parent Study'. It involves observing these patients over time.

Participant Groups

Group I: E9: Cabozantinib Monotherapy Experimental Treatment 1 Intervention

Group II: E8: Capecitabine Monotherapy Experimental Treatment 1 Intervention

Group III: E7: Rucaparib Monotherapy Experimental Treatment 1 Intervention

Group IV: E6: Sunitinib Monotherapy Experimental Treatment 1 Intervention

Group V: E5: Enzalutamide Monotherapy Experimental Treatment 1 Intervention

Group VI: E4: Leucovorin + Oxaliplatin + Fluorouracil Experimental Treatment 3 Interventions

Group VII: E3: Leucovorin + Fluorouracil Experimental Treatment 1 Intervention

Group VIII: E2: Regorafinib Monotherapy Experimental Treatment 1 Intervention

Group IX: E1: Bevacizumab Monotherapy Experimental Treatment 1 Intervention

Group X: E11: Pembrolizumab Monotherapy Experimental Treatment 1 Intervention

Group XI: E10: Pemetrexed Monotherapy Experimental Treatment 1 Intervention

Group XII: D4: Nivolumab + Bevacizumab Experimental Treatment 1 Intervention

Group XIII: D3: Nivolumab + Daratumumab Experimental Treatment 2 Interventions

Group XIV: D2: Nivolumab + Rucaparib Experimental Treatment 2 Interventions

Group XV: D1: Nivolumab + Temozolomide Experimental Treatment 2 Interventions

Group XVI: C9: Relatlimab + Nivolumab SAV + Bevacizumab Experimental Treatment 3 Interventions

Group XVII: C8: Relatlimab + Nivolumab SAV + PDCT Dose 1 Experimental Treatment 2 Interventions

Group XVIII: C7: Relatlimab + Nivolumab SAV Dose 3 Experimental Treatment 2 Interventions

Group XIX: C6: Relatlimab + Nivolumab + Capecitabine Experimental Treatment 2 Interventions

Group XX: C5: Relatlimab + Nivolumab + Ipilimumab Experimental Treatment 2 Interventions

Group XXI: C4: Relatlimab + Nivolumab SAV Dose 2 Experimental Treatment 2 Interventions

Group XXII: C3: Relatlimab + Nivolumab Fixed Dose Combination Dose 2 Experimental Treatment 1 Intervention

Group XXIII: C2: Relatlimab + Nivolumab Single Agent Vial (SAV) Dose 1 Experimental Treatment 2 Interventions

Group XXIV: C1: Relatlimab + Nivolumab Fixed Dose Combination Dose 1 Experimental Treatment 1 Intervention

Group XXV: C12: Relatlimab + Nivolumab SAV Dose 5 Experimental Treatment 2 Interventions

Group XXVI: C11: Relatlimab + Nivolumab SAV + PDCT Dose 2 Experimental Treatment 2 Interventions

Group XXVII: C10: Relatlimab + Nivolumab SAV Dose 4 Experimental Treatment 2 Interventions

Group XXVIII: B3: Nivolumab + Ipilimumab + Trametinib Experimental Treatment 3 Interventions

Group XXIX: B2: Nivolumab + Ipilimumab + Cabozantinib Experimental Treatment 3 Interventions

Group XXX: B1: Nivolumab + Ipilimumab Experimental Treatment 2 Interventions

Group XXXI: A2: Nivolumab Monotherapy Dose 2 Experimental Treatment 1 Intervention

Group XXXII: A1: Nivolumab Monotherapy Dose 1 Experimental Treatment 1 Intervention

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

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

MBA from ESADE Business School

John (Jack) Lawrence

Janssen Pharmaceuticals

Chief Medical Officer since 2023

MD from University of Virginia School of Medicine

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Clovis Oncology, Inc.

Industry Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

Findings from Research

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]

In a phase III trial, nivolumab significantly improved health-related quality of life (HRQoL) and disease-related symptoms compared to docetaxel in patients with advanced non-squamous non-small cell lung cancer, with improvements noted at multiple time points (weeks 12, 24, 30, and 42).

Patients receiving nivolumab experienced a longer time to first deterioration in HRQoL compared to those treated with docetaxel, indicating a more favorable safety profile and sustained symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Reck, M., Brahmer, J., Bennett, B., et al.[2019]

In a study of 52 patients with advanced non-small-cell lung cancer (NSCLC) treated with nivolumab, the drug demonstrated a 23.1% overall response rate and a 1-year overall survival rate of 59.9%, indicating its efficacy in a real-world setting.

Nivolumab had a manageable safety profile, with immune-related adverse events occurring in 38.5% of patients, all of whom recovered after treatment; additionally, a high pretreatment neutrophil-to-lymphocyte ratio (NLR ≥ 5) was linked to poorer prognosis, suggesting it could serve as a predictive marker for survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Nivolumab and Utility of Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Advanced Non-Small-Cell Lung Cancer: A Prospective Observational Study. Fukui, T., Okuma, Y., Nakahara, Y., et al.[2022]

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]

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 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]

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

In a meta-analysis of five studies involving 2399 patients, nivolumab was found to significantly lower the risk of hematological toxicities such as anemia, neutropenia, and leukopenia compared to other treatments.

The relative risks for these conditions were notably low, indicating that nivolumab may be a safer option regarding hematological side effects, which is important for clinicians when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. Shi, Z., Liu, X., Chen, M., et al.[2023]

In a study of 45 patients with metastatic melanoma treated with the combination of nivolumab and ipilimumab, the disease control rate was 54% and the objective response rate was 29%, indicating moderate efficacy in a real-world setting.

The treatment had a high toxicity profile, with 88% of patients experiencing adverse events, and 44% discontinuing treatment due to these events, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. Parakh, S., Randhawa, M., Nguyen, B., et al.[2019]

Nivolumab, a PD-1 inhibitor used for cancer treatment, can lead to serious adverse effects such as diabetic ketoacidosis, as demonstrated in a case involving a 69-year-old woman with lung cancer who developed this condition shortly after starting treatment.

Routine monitoring of blood glucose and HbA1c levels is crucial for patients receiving nivolumab to prevent diabetic ketoacidosis, and treatment should only be initiated if the patient's glucose levels are stable, highlighting the need for careful management and patient education.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetic ketoacidosis induced by nivolumab in invasive mucinous adenocarcinoma of the lung: a case report and review of the literature. Yan, J., Xie, ZZ., Moran, T., et al.[2022]

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 (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, 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 79 pre-treated patients with advanced non-small cell lung cancer, nivolumab significantly prolonged progression-free survival, especially in patients who had a partial response to prior treatments.

The occurrence of skin rash during nivolumab treatment was associated with improved long-term survival, suggesting that this side effect may indicate a favorable response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases. Akano, Y., Kuribayashi, K., Funaguchi, N., et al.[2020]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. [2019]

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

Activity of Nivolumab and Utility of Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Advanced Non-Small-Cell Lung Cancer: A Prospective Observational Study. [2022]

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

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

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

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

6. United States 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]

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

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis. [2023]

9. Australia pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. [2019]

10. China pubmed.ncbi.nlm.nih.gov

Diabetic ketoacidosis induced by nivolumab in invasive mucinous adenocarcinoma of the lung: a case report and review of the literature. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

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

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

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

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

14. Greece pubmed.ncbi.nlm.nih.gov

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases. [2020]