Intralesional Nivolumab for Precancerous Conditions

Overseen By Moran Amit, MD, PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antineoplastics, Monoclonal antibodies

Disqualifiers: Active TB, Active infection, 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: 12 weeks

45 Participants Needed

Trial Summary

What is the purpose of this trial?

To evaluate the antitumor efficacy of intralesional injections of nivolumab in patients with high-risk oral premalignant lesions

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 currently receiving any study therapy with potential anti-cancer activity or have had recent chemotherapy, targeted therapy, or radiation therapy, you may not be eligible to participate.

What data supports the effectiveness of the drug Nivolumab for precancerous conditions?

Nivolumab has shown effectiveness in treating advanced lung cancer and melanoma by improving survival rates and tumor response. This suggests it may have potential benefits for other conditions, including precancerous ones, due to its ability to enhance the immune system's ability to fight abnormal cells. ^{1 2 3 4 5}

Is intralesional Nivolumab safe for humans?

There is no specific safety data for intralesional Nivolumab, but a similar treatment, intralesional pembrolizumab, was found to be safe and well-tolerated in patients with ductal carcinoma in situ (a type of breast condition). ^{6 7 8 9 10}

How is the drug Nivolumab unique for treating precancerous conditions?

Nivolumab is unique because it is an immune checkpoint inhibitor that targets the PD-1 pathway, helping the immune system recognize and attack abnormal cells. Unlike traditional treatments, it is administered directly into the lesion (intralesional), which may offer a more targeted approach for precancerous conditions. ^{1 3 4 5 11}

Research Team

Moran Amit, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for individuals with high-risk oral premalignant lesions, which are early signs that may lead to cancer. Specific eligibility criteria details are not provided.

Inclusion Criteria

1. Presence of a treatment naïve, biopsy proven, intraoral premalignant lesion visible from oral cavity.

2. Be willing and able to provide written informed consent for the trial. In the event that non-English speaking participants are eligible for this study, a short form (if applicable) or an ICD in their language, will be utilized and completed in accordance with the MDACC "Policy For Consenting Non-English Speaking Participants."

4. Be willing to provide tissue, either archive or from a newly obtained oral biopsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intralesional injections of nivolumab or placebo for high-risk oral premalignant lesions

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Nivolumab

Trial Overview The study tests the effectiveness of nivolumab, an immunotherapy drug, administered directly into the lesion in the mouth to see if it can prevent these early signs from developing into cancer.

Participant Groups

Group I: Nivolumab/Placebo Experimental Treatment 1 Intervention

Participants will be screened for LOH and randomly assigned to trial

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

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 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 (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]

Nivolumab, a monoclonal antibody targeting the programmed death receptor-1, has shown promising efficacy in treating advanced malignant melanoma, with nearly 25% of patients achieving a partial tumor response in a phase II trial involving previously treated stage III/IV patients.

The treatment demonstrated a durable clinical benefit, with a median progression-free survival of 172 days and an acceptable safety profile, as less than 18% of patients experienced severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review of its use in patients with malignant melanoma. Deeks, ED.[2021]

The study demonstrated that intralesional injections of the PD-1 inhibitor pembrolizumab are safe and well-tolerated in patients with high-risk ductal carcinoma in situ (DCIS), with significant increases in total and CD8+ T cell populations observed after treatment.

Despite the robust immune response, there was no significant change in tumor volume or evidence of cell death, indicating that while pembrolizumab can enhance T cell activity, additional strategies may be necessary to improve anti-tumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of the immune microenvironment of high-risk ductal carcinoma in situ by intralesional pembrolizumab injection. Glencer, AC., Wong, JM., Hylton, NM., et al.[2023]

In a study of 14,419 women treated for ductal carcinoma in situ (DCIS) in the Netherlands, those who underwent breast-conserving surgery (BCS) alone had a higher risk of developing ipsilateral invasive breast cancer (iIBC) compared to those who received BCS plus radiotherapy (RT), with a cumulative incidence of 7.1% versus 3.1% after 10 years.

The risk of iIBC remained significantly elevated in the BCS alone group for at least 10 years post-treatment, indicating that adding radiotherapy after BCS may provide a protective effect against the development of invasive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of contemporary treatment of DCIS on the risk of developing an ipsilateral invasive Breast cancer (iIBC) in the Dutch population. Alaeikhanehshir, S., Schmitz, RSJM., van den Belt-Dusebout, AW., et al.[2023]

In situ breast cancer is being diagnosed more frequently due to better screening methods, but treatment options remain controversial, especially regarding the balance between effective therapy and preserving breast appearance.

Ongoing studies like the NSABP B-17 trial aim to clarify the best treatment approaches for ductal and lobular carcinoma in situ, helping oncologists make informed decisions that consider patient preferences and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vexed surgeons, perplexed patients, and breast cancers which may not be cancer. Ketcham, AS., Moffat, FL.[2019]

In a study of 73 BRCA1/2-associated breast cancers compared to 146 sporadic cases, 59% of BRCA1/2 tumors had preinvasive lesions, indicating that these cancers can develop through similar pathways as sporadic cancers.

The most common preinvasive lesion found was ductal carcinoma in situ (DCIS), which was present in 56% of BRCA1/2-associated cancers, suggesting that DCIS should be recognized as part of the tumor spectrum for BRCA1/2 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High prevalence of preinvasive lesions adjacent to BRCA1/2-associated breast cancers. Arun, B., Vogel, KJ., Lopez, A., et al.[2021]

Certain benign breast lesions, such as atypical ductal hyperplasia and lobular carcinoma in situ, have significant premalignant potential and can evolve into invasive breast cancer over time.

Advancements in molecular genetics are helping researchers understand the diverse genetic mechanisms behind breast cancer development, which may lead to targeted prevention strategies for premalignant lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Premalignant and in situ breast disease: biology and clinical implications. Arpino, G., Laucirica, R., Elledge, RM.[2019]

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

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

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

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

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

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

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

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

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

Nivolumab: a review of its use in patients with malignant melanoma. [2021]

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

Modulation of the immune microenvironment of high-risk ductal carcinoma in situ by intralesional pembrolizumab injection. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The effects of contemporary treatment of DCIS on the risk of developing an ipsilateral invasive Breast cancer (iIBC) in the Dutch population. [2023]

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

Vexed surgeons, perplexed patients, and breast cancers which may not be cancer. [2019]

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

High prevalence of preinvasive lesions adjacent to BRCA1/2-associated breast cancers. [2021]

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

Premalignant and in situ breast disease: biology and clinical implications. [2019]

11. 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]