Nimotuzumab and Nivolumab in Treating Patients With Advanced Non-small Cell Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must not be taking: Antibiotics, Antivirals, Antifungals, others

Disqualifiers: Autoimmune, Infections, Brain metastases, others

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

Compensation: Varies

Number of Visits: 3

Duration: 28 days per cycle

7 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing nimotuzumab and nivolumab, two drugs that help the immune system fight cancer. It targets patients with advanced non-small cell lung cancer that has spread and is hard to treat. These drugs work by helping the immune system recognize and attack cancer cells. Nivolumab is an immune checkpoint inhibitor that has shown promise in treating various cancers, including non-small cell lung cancer (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, you cannot receive other anti-cancer treatments during the study, except for nimotuzumab or nivolumab.

What data supports the effectiveness of the drug Nivolumab?

Nivolumab has shown effectiveness in treating advanced non-small-cell lung cancer (NSCLC) by improving survival rates and response duration compared to other treatments like docetaxel. It has also been used successfully in advanced squamous NSCLC, providing better overall survival and being better tolerated than some other chemotherapy options. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Nivolumab, also known as Opdivo, has been studied in many clinical trials and is generally considered safe, but it can cause side effects. Common side effects include tiredness, skin rash, itching, diarrhea, and nausea. Serious side effects are less common but can include issues with the immune system affecting organs like the colon and lungs. ^{6 7 8 9 10}

How does the drug combination of Nimotuzumab and Nivolumab differ from other treatments?

Nivolumab is a unique drug because it is an immune checkpoint inhibitor that targets the PD-1 receptor, helping the immune system recognize and attack cancer cells. This mechanism is different from traditional chemotherapy, which directly kills cancer cells. Nimotuzumab, often used in combination, is an antibody that targets a specific protein on cancer cells, potentially enhancing the immune response initiated by Nivolumab. ^{4 11 12 13 14}

Research Team

Grace Dy

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

Inclusion Criteria

You are expected to live for at least 3 more months.

Patients with pathologically confirmed non-small cell lung cancer

Have measurable disease per RECIST 1.1 criteria present

Exclusion Criteria

You are allergic to the ingredients in the study drugs or similar medicines.

You have a heart problem that is not under control or you have trouble with your heart's function.

You have a history of severe chest pain that cannot be controlled with medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab and nimotuzumab intravenously on days 1 and 15, with courses repeating every 28 days in the absence of disease progression or unacceptable toxicity

28 days per cycle

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days after last dose, then every 12 weeks

1 visit at 30 days, then every 12 weeks (in-person)

Treatment Details

Interventions

• Nimotuzumab
• Nivolumab

Participant Groups

Group I: Treatment (nivolumab, nimotuzumab) Experimental Treatment 3 Interventions

Patients receive nivolumab IV over 60 minutes and nimotuzumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Findings from Research

In a study of patients with advanced gastric cancer, nivolumab (NIVO) showed a higher objective response rate (20%) compared to irinotecan (IRI) (6%), although both treatments had similar overall survival rates of 6.4 months.

Nivolumab demonstrated a better safety profile, with significantly fewer severe adverse events, such as neutropenia (3% for NIVO vs. 28% for IRI), indicating it may be a safer option for patients despite similar efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus irinotecan as third- or later-line treatment for advanced gastric cancer: a multi-center retrospective study. Kumanishi, R., Kadowaki, S., Mitani, S., et al.[2023]

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]

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]

In a subgroup analysis of the CheckMate 025 study involving 406 patients with advanced renal cell carcinoma, 48% of those who progressed by RECIST criteria continued treatment with nivolumab and showed a 13% rate of tumor burden reduction post-progression.

Patients who continued nivolumab treatment beyond RECIST progression had a lower incidence of treatment-related adverse events after progression (59%) compared to before (71%), indicating a favorable safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. Escudier, B., Motzer, RJ., Sharma, P., et al.[2022]

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 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]

Checkpoint inhibitors like nivolumab and pembrolizumab can lead to autoimmune side effects, including immune thrombocytopenia, which was observed in a patient with metastatic melanoma shortly after starting treatment.

Unlike chemotherapy-induced cytopenia, which is caused by bone marrow toxicity, thrombocytopenia from checkpoint inhibitors is primarily autoimmune in nature, highlighting the need for careful monitoring and immune testing during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Immune Thrombocytopenia as a Rare Side Effect of an Immunotherapy with PD1-Blocking Agents for Metastatic Melanoma. Pföhler, C., Eichler, H., Burgard, B., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., 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, 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]

References

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

Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

Nivolumab versus irinotecan as third- or later-line treatment for advanced gastric cancer: a multi-center retrospective study. [2023]

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

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

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. [2022]

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. England pubmed.ncbi.nlm.nih.gov

Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Nivolumab and immune-mediated colitis. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

A Case of Immune Thrombocytopenia as a Rare Side Effect of an Immunotherapy with PD1-Blocking Agents for Metastatic Melanoma. [2022]

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

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]

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

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

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

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

13. England pubmed.ncbi.nlm.nih.gov

Metastatic small cell neuroendocrine carcinoma of the cervix treated with the PD-1 inhibitor, nivolumab: a case report. [2022]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab. [2020]