Nivolumab +/- Ipilimumab for Anal Cancer

Not currently recruiting at 64 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: HAART

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of the drugs nivolumab and ipilimumab for individuals with anal canal cancer that hasn't responded to previous treatment and has metastasized. These drugs are a type of immunotherapy, helping the body's immune system combat cancer. The trial consists of different parts: some participants will receive nivolumab alone, while others will receive both nivolumab and ipilimumab. Suitable candidates have anal cancer that continues to grow despite past treatments and has spread to other areas. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering access to potentially effective therapies.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must wait at least 28 days after completing chemotherapy or radiotherapy before starting the trial treatment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nivolumab is generally well-tolerated by patients with metastatic anal cancer that hasn't responded to other treatments. In one study, some patients experienced a reduction in their cancer, with a 24% overall response rate.

When combined with ipilimumab, studies indicate that nivolumab can be more effective than when used alone. Patients taking both drugs had a 38% lower risk of their cancer worsening or leading to death compared to those taking only nivolumab. This combination is considered safe and has been successfully used for other types of cancer.

Both treatments have been used in other contexts and have demonstrated manageable safety profiles, meaning they usually don't cause severe side effects that can't be managed. However, like any treatment, some side effects can occur, so discussing potential risks with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Nivolumab and Ipilimumab for anal cancer because these drugs work by harnessing the body's immune system to fight cancer cells, a method known as immunotherapy. Unlike traditional chemotherapy, which directly targets and kills cancer cells, Nivolumab blocks a protein called PD-1, helping the immune system recognize and attack cancer cells more effectively. Ipilimumab also enhances immune response by targeting a different protein called CTLA-4. This dual-action approach offers a novel mechanism that could potentially lead to better outcomes for patients compared to conventional treatments.

What evidence suggests that this trial's treatments could be effective for anal cancer?

Research has shown that nivolumab, a treatment for advanced anal cancer, holds promise. It helped 24.3% of patients whose cancer had been previously treated by shrinking or slowing the disease. On average, patients experienced 4.1 months without cancer progression and lived about 11.5 months after starting treatment. In this trial, some participants will receive nivolumab alone.

Others will receive a combination of nivolumab and ipilimumab, another drug that aids the immune system. Studies have shown that 71% of patients responded to this combination, which is more effective than nivolumab alone. This combination has demonstrated lasting benefits in other types of cancer, suggesting it could be beneficial for anal cancer as well. These treatments work by enabling the immune system to attack and slow cancer growth. ^{1 2 5 6 7}

Who Is on the Research Team?

Cathy Eng

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with metastatic anal canal cancer that hasn't improved after treatment. Participants must have adequate organ function, agree to contraception, and be willing to undergo HIV/hepatitis testing. Exclusions include recent chemotherapy, other investigational drugs, allergies to similar compounds, uncontrolled illnesses, certain prior cancers unless in remission for three years or more.

Inclusion Criteria

My cancer can be measured by scans and was checked within the last 28 days.

I am fully active or have some restrictions but can still care for myself.

I have had at least one treatment for advanced anal cancer that cannot be cured.

Exclusion Criteria

I haven't taken high-dose steroids or immunosuppressants in the last 14 days.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab and/or ipilimumab

I have previously been treated with specific immunotherapy drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab with or without ipilimumab intravenously, with regular imaging and blood sample collection to monitor response and toxicity

Up to 2 years

Bi-weekly to monthly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

100 days post-treatment, then every 3 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The study examines the effectiveness of nivolumab alone or combined with ipilimumab in treating refractory metastatic anal canal cancer. These are immunotherapy drugs designed to help the immune system fight cancer by blocking tumor growth and spread.

How Is the Trial Designed?

Group I: Part B Arm II (nivolumab, ipilimumab) Experimental Treatment 5 Interventions

Patients receive nivolumab as in Arm I. Patients also receive ipilimumab IV over 30 minutes once every 8 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.

Group II: Part B Arm I (nivolumab) Experimental Treatment 4 Interventions

Patients receive nivolumab IV over 30 minutes once every 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.

Group III: Part A (nivolumab) Experimental Treatment 4 Interventions

Patients receive nivolumab IV over 60 minutes once every two weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ipilimumab, an anti-CTLA-4 monoclonal antibody, is a significant advancement in cancer immunotherapy, effectively targeting T-cell inhibitory checkpoints to enhance the immune response against tumors.

In a review of 44 prostate cancer patients treated with ipilimumab, it was found that while the therapy is effective, it is also associated with immune-related adverse events (irAEs) that require careful management with immunosuppressive agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience. Gao, J., He, Q., Subudhi, S., et al.[2022]

In a study of 274 elderly patients with advanced melanoma, the risk of developing colitis was similar for those treated with anti-CTLA4 (ipilimumab) and anti-PD1 (nivolumab or pembrolizumab) therapies.

However, when considering patients across all stages of melanoma, anti-PD1 treatment was associated with a significantly lower risk of colitis compared to anti-CTLA4, suggesting a safer profile for anti-PD1 in this broader patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of immune-checkpoint inhibitors and the risk of immune-related colitis among elderly patients with advanced melanoma: real-world evidence from the SEER-Medicare database. Almutairi, AR., Slack, M., Erstad, BL., et al.[2022]

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

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 combined with ipilimumab significantly improves overall survival in adult patients with intermediate/poor-risk advanced renal cell carcinoma compared to sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

In the study involving 1096 patients, the median overall survival was not reached for the nivolumab + ipilimumab group, while it was 25.95 months for the sunitinib group, highlighting the potential of this combination therapy for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. Ali, S., Camarero, J., Hennik, P., et al.[2021]

In a review of 129 oncology patients treated with immune checkpoint inhibitors, 51.9% experienced at least one immune-related adverse event (irAE), highlighting the common occurrence of these side effects.

Nearly half of the irAEs were managed according to established guidelines, but there was significant variability in documentation and management practices, indicating a need for improved adherence as immunotherapy use increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events. Teimouri, A., Minard, LV., Scott, SN., et al.[2022]

In a phase 1 trial involving 53 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 40% objective response rate, with 65% of patients showing clinical activity, indicating significant effectiveness in tumor reduction.

The concurrent treatment had a manageable safety profile, with 53% of patients experiencing grade 3 or 4 adverse events, which were similar to those seen with monotherapy and generally reversible, suggesting that this combination therapy is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in advanced melanoma. Wolchok, JD., Kluger, H., Callahan, MK., et al.[2022]

A meta-analysis of gastrointestinal adverse events in patients treated for malignant tumors with nivolumab and ipilimumab found that diarrhea was the most common side effect, along with nausea and decreased appetite.

Severe gastrointestinal issues, particularly colitis and diarrhea, were identified as significant risks, suggesting that adjusting the administration scheme of the treatment could help reduce these adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related gastrointestinal adverse events of nivolumab plus ipilimumab in randomized clinical trials: a systematic review and meta-analysis. Liu, K., Wang, YH., Luo, N., et al.[2023]

A meta-analysis of 21 trials involving 11,454 patients found that immune checkpoint inhibitors (ICIs) significantly increase the risk of various immune-related adverse events (irAEs), including colitis, liver enzyme elevation, rash, hypothyroidism, and pneumonitis compared to non-ICI treatments.

While the incidence of fatal irAEs was less than 1%, the study highlights the importance of early recognition and intervention for these adverse events to prevent complications, particularly noting that ipilimumab was linked to a higher risk of certain skin and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients. De Velasco, G., Je, Y., Bossé, D., et al.[2023]

In a study of 1266 anal cancer patients treated according to Nordic guidelines, the 3-year recurrence-free survival rate was between 63% and 76%, indicating effective treatment outcomes.

Factors such as older age, male gender, and larger tumors were linked to worse outcomes, and the study suggests that inguinal prophylactic irradiation should be considered even for small tumors to reduce recurrence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anal carcinoma - Survival and recurrence in a large cohort of patients treated according to Nordic guidelines. Leon, O., Guren, M., Hagberg, O., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5809128/

Nivolumab for previously treated unresectable metastatic anal ... Although the median progression-free survival was 4.1 months, the longest duration of treatment has been almost 1 year and is continuing as of the data cutoff ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e15502

Efficacy and safety of nivolumab in pretreated patients with ... Nivolumab was administered as a 2nd line treatment in 13 pts, while 2 pts received ICI in the 3rd line. Overall, median OS was 8.3 months (mo.) ...

3. onclive.com onclive.com/view/nivolumab-effective-in-advanced-anal-cancer

Nivolumab Effective in Advanced Anal Cancer Treatment with the PD-1 inhibitor nivolumab (Opdivo) resulted in an overall response rate of 24.3% in previously treated patients with squamous cell carcinoma ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949819825000494

Advances in anal cancer treatment: current standards, the ... From the 37 patients treated with nivolumab, 9 had radiographic responses (ORR 24%). Median PFS was 4.1 months, and median OS was 11.5 months.

5. opdivohcp.com opdivohcp.com/efficacy/crc

Efficacy Data for Colorectal Cancer (CRC) - Opdivo In Checkmate 9LA, the most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased ...

6. news.bms.com news.bms.com/news/details/2025/U-S--Food-and-Drug-Administration-Approves-Opdivo-nivolumab-plus-Yervoy-ipilimumab-as-a-Treatment-for-Patients-with-Previously-Untreated-Microsatellite-Instability-High-or-Mismatch-Repair-Deficient-Unresectable-or-Metastatic-Colorectal-Cancer1/default.aspx

U.S. Food and Drug Administration Approves Opdivo ... In the CheckMate-8HW trial, Opdivo plus Yervoy demonstrated a 38% reduction in the risk of disease progression or death vs. Opdivo monotherapy ...

7. opdivo.com opdivo.com/clinical-trial-results

Clinical Trial Results Select your cancer type above to see how OPDIVO, alone or in combination with other therapies, performed in clinical trials.