Nimotuzumab + Nivolumab for 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and side effects of two drugs, nimotuzumab and nivolumab, for treating advanced non-small cell lung cancer that has spread and is difficult to treat. These monoclonal antibodies target specific cells to block tumor growth. The trial is intended for individuals whose lung cancer has progressed after initial chemotherapy. Participants should have a type of lung cancer that has worsened after certain treatments and must be able to provide tissue samples for testing. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

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.

Is there any evidence suggesting that nimotuzumab and nivolumab are likely to be safe for humans?

Research has shown that nimotuzumab is generally safe and well-tolerated. Studies have found no additional side effects, such as allergic reactions or skin changes, when using nimotuzumab. It has been tested with other cancer drugs without major safety concerns.

Nivolumab is already approved for treating other cancers. Studies indicate that common side effects include tiredness, rash, and diarrhea, affecting about 20% or more of patients. While generally safe, nivolumab can cause these reactions.

Both treatments have undergone testing and are considered safe for further evaluation in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of nimotuzumab and nivolumab for advanced non-small cell lung cancer because these treatments target the disease in unique ways. Unlike current treatments, which often rely on chemotherapy, nimotuzumab is a monoclonal antibody that specifically targets the epidermal growth factor receptor (EGFR), potentially reducing cancer growth. Nivolumab, on the other hand, is an immunotherapy drug that helps the immune system recognize and attack cancer cells by blocking the PD-1 pathway. Together, these treatments offer a promising approach by combining targeted therapy with immunotherapy, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that nivolumab can help treat advanced non-small-cell lung cancer (NSCLC) by increasing survival rates and extending the duration of treatment effectiveness. Studies have found that nivolumab, particularly when combined with other treatments, can improve survival chances for lung cancer patients. Nimotuzumab targets specific cells to inhibit tumor growth. Although limited data exists on using nimotuzumab and nivolumab together specifically for NSCLC, research in similar cancers suggests they might have positive effects. Early results from other trials indicate that this combination, which participants in this trial will receive, may help slow tumor growth by targeting cancer cells. ^{6 7 8 9 10}

Who Is on the Research Team?

Grace Dy

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Nimotuzumab
• Nivolumab

How Is the Trial Designed?

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+

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, 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 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]

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]

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, 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02947386

Nimotuzumab and Nivolumab in Treating Patients With ... This phase I/II trial studies the best dose and side effects of nimotuzumab when giving together with nivolumab and to see how well they work in treating ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7186663/

Response to nivolumab combining radiotherapy and ... This is the first case describing the efficacy and safety of nivolumab plus radiotherapy and nimotuzumab in an OSCC patient with a strong PD-L1 expression, ...

3. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/clinical-trial-data-presented-at-asco-show-efficacy-of-opdivo-based-combinations-treating-lung-cancer

Clinical Trial Data Presented at ASCO Show Efficacy of ... Results of the Phase III CheckMate -77T, CheckMate -816, and CheckMate -9LA trials show the potential of Opdivo to improve survival among ...

4. withpower.com withpower.com/trial/phase-2-carcinoma-non-small-cell-lung-5-2017-6dbe2

Nimotuzumab and Nivolumab in Treating Patients With ... Nivolumab has shown effectiveness in treating advanced non-small-cell lung cancer (NSCLC) by improving survival rates and response duration compared to other ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2016-01476

Nimotuzumab and Nivolumab in Treating Patients with ... This phase I/II trial studies the best dose and side effects of nimotuzumab when giving together with nivolumab and to see how well they work in treating ...

6. file.medchemexpress.com file.medchemexpress.com/batch_PDF/HY-P9968/Nimotuzumab-SDS-MedChemExpress.pdf

Safety Data Sheet Rinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician. Inhalation. Safety Data Sheet.

7. abmole.com abmole.com/literature/nimotuzumab-msds.html?srsltid=AfmBOop62Nsm3wEJN7l76BMod28C7Sh70hsKGkMg8H-IpxtFAnNxZqJc

Material Safety Data Sheet of Nimotuzumab Avoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation. 7.2, Conditions for safe ...

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2006.24.18_suppl.12504

Safety, efficacy and pharmacokinetics of nimotuzumab, a ... Conclusions: These data confirm that nimotuzumab is safe and well tolerated. To improve efficacy, a combination trial with gemcitabine is ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)38345-9/fulltext

Safety and efficacy of nimotuzumab with concurrent ... Nimotuzumab was observed to be safe with no additional adverse events (hypersensitivity, allergic reaction and skin changes) were reported during the study ...

10. theracim-nimotuzumab.com theracim-nimotuzumab.com/efficacy-safety-data/

Efficacy & Safety Data - Nimotuzumab (TheraCIM® h-R3) EFFICACY & SAFETY DATA · Locally Advanced Head and Neck Squamous Cell Carcinoma · Locally Advanced Nasopharyngeal Cancer · High Grade Glioma · Locally Advanced or ...