Nivolumab +/− Ipilimumab for Ovarian Cancer

Recruiting at 232 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Organ transplant, Pregnancy, 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: 28

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies how well nivolumab works with or without ipilimumab in treating patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer that has not responded after prior treatment (persistent) or has come back (recurrent). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Do I need to stop my current medications to join the trial?

The trial requires that any hormonal therapy for the cancer be stopped at least one week before joining, and any other cancer treatments like chemotherapy or immunotherapy be stopped at least four weeks before. If you're on other medications not related to cancer treatment, the protocol doesn't specify, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug combination Nivolumab and Ipilimumab for ovarian cancer?

The combination of Nivolumab and Ipilimumab has shown durable and long-term effectiveness in treating advanced non-small cell lung cancer, suggesting potential benefits for other cancers. Additionally, immune checkpoint inhibitors like these are being explored for ovarian cancer due to their ability to help the immune system fight cancer cells. ^{1 2 3 4 5}

Is the combination of Nivolumab and Ipilimumab safe for treating ovarian cancer?

The combination of Nivolumab and Ipilimumab, used in treating ovarian cancer, can lead to immune-related side effects, which are different from those seen with traditional chemotherapy. It's important to recognize and manage these side effects early to ensure patient safety. ^{3 5 6 7 8}

How is the drug combination of Nivolumab and Ipilimumab unique for treating ovarian cancer?

The combination of Nivolumab and Ipilimumab is unique because it uses two drugs that work together to boost the immune system's ability to fight cancer, which is different from traditional chemotherapy. Nivolumab blocks a protein called PD-1 on immune cells, while Ipilimumab blocks another protein called CTLA-4, both of which help the immune system attack cancer cells more effectively. ^{2 3 4 5 9}

Research Team

Dimitry Zamarin

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for patients with persistent or recurrent ovarian, primary peritoneal, or fallopian tube cancer who've had prior treatment. They should have adequate organ function and no active infections. Excluded are those with HIV not well-managed by HAART, severe allergies to monoclonal antibodies, recent other cancers (except breast cancer within 2 years), brain disease, uncontrolled illnesses, or a history of certain autoimmune diseases.

Inclusion Criteria

Creatinine =< 1.5 x institutional/laboratory ULN (within 14 days prior to registration)

LVEF >= 50% (measured within 28 days of study entry)

Adequate oxygen saturation via pulse oximeter within 28 days prior to registration

Exclusion Criteria

You are pregnant or breastfeeding.

No planned concomitant, non-protocol directed anti-cancer therapy

Severe hypersensitivity reaction to any monoclonal antibody

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive nivolumab with or without ipilimumab. Treatment repeats every 3 weeks for 4 cycles or every 4 weeks for 2 cycles depending on the group.

6-12 weeks

4 visits (in-person)

Maintenance

Patients receive nivolumab every 2 weeks. Treatment repeats every 4 weeks for up to 21 cycles.

84 weeks

21 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

5 years

Every 3 months for 2 years, then every 6 months for 3 years

Treatment Details

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The study tests how effective nivolumab is alone or combined with ipilimumab in treating these cancers. Both drugs are immunotherapies that may boost the body's ability to fight cancer by interfering with tumor growth and spread.

Participant Groups

Group I: Group II (nivolumab, ipilimumab) Experimental Treatment 2 Interventions

INDUCTION: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive nivolumab IV over 30 minutes every 2 weeks. Treatment repeats every 4 weeks for up to 21 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Group I (nivolumab) Active Control 1 Intervention

INDUCTION: Patients receive nivolumab IV over 30 minutes every 2 weeks. Treatment repeats every 4 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive nivolumab IV over 30 minutes every 2 weeks. Treatment repeats every 4 weeks for up to 21 cycles in the absence of disease progression or unacceptable toxicity.

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+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

Epithelial ovarian cancer (EOC) has a high recurrence rate of about 70% after standard treatment, highlighting the urgent need for new therapies to improve patient survival.

Immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1 antibodies, are being explored as potential treatments for EOC due to the cancer's strong immunogenicity, but further research is necessary to understand their effectiveness and identify which patients may benefit most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors: A New Opportunity in the Treatment of Ovarian Cancer? Mittica, G., Genta, S., Aglietta, M., et al.[2022]

In a phase III study involving 316 patients with platinum-resistant ovarian cancer, nivolumab did not improve overall survival compared to chemotherapy (gemcitabine or pegylated liposomal doxorubicin), with median overall survival of 10.1 months for nivolumab versus 12.1 months for chemotherapy.

Nivolumab was associated with fewer treatment-related adverse events (61.5% vs. 98.1% for chemotherapy), indicating it may be better tolerated, but it also showed worse progression-free survival (2.0 months vs. 3.8 months for chemotherapy).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). Hamanishi, J., Takeshima, N., Katsumata, N., et al.[2023]

In a study of 100 women with recurrent epithelial ovarian cancer, the combination of ipilimumab and nivolumab resulted in a significantly higher response rate (31.4%) compared to nivolumab alone (12.2%), indicating improved efficacy of the combination therapy.

The median progression-free survival was also longer for the combination group (3.9 months) compared to nivolumab alone (2 months), although both treatments had similar rates of severe adverse events, suggesting that the combination therapy is relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Nivolumab Versus Nivolumab and Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study. Zamarin, D., Burger, RA., Sill, MW., et al.[2021]

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]

In a study of 44 women with recurrent ovarian cancer treated with immune checkpoint inhibitors, the overall response rate was 14.2%, with a notable correlation between platinum sensitivity and response in high-grade serous ovarian cancer (HGSOC) patients.

Severe immune-related adverse events (irAEs) occurred in 47.7% of patients, with elevated hepatic or pancreatic enzymes being the most common, and a higher number of gene mutations appeared to protect against these specific adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. Hinchcliff, E., Hong, D., Le, H., et al.[2023]

Immune checkpoint inhibitors, which target specific proteins like CTLA-4 and PD-1, have significantly improved survival rates for patients with advanced solid tumors, including ovarian cancer.

The report emphasizes the need for early recognition and management of immune-related adverse events, which differ from those seen with traditional chemotherapy, highlighting the unique challenges of immunotherapy in treating gynecologic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and Management of Immune Checkpoint Inhibitor-related Toxicities in Ovarian Cancer: A Series of Case Vignettes. Johnson, C., Jazaeri, AA.[2019]

The combination of pembrolizumab and carboplatin was found to be well-tolerated and showed activity in patients with recurrent platinum-resistant ovarian cancer, with a median overall survival of 11.3 months.

Patients with a higher ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden had significantly longer overall survival, suggesting this ratio could help identify those who may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. Liao, JB., Gwin, WR., Urban, RR., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors: A New Opportunity in the Treatment of Ovarian Cancer? [2022]

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

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). [2023]

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

Randomized Phase II Trial of Nivolumab Versus Nivolumab and Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study. [2021]

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

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

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

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials. [2023]

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

Diagnosis and Management of Immune Checkpoint Inhibitor-related Toxicities in Ovarian Cancer: A Series of Case Vignettes. [2019]

7. England pubmed.ncbi.nlm.nih.gov

The role of immune checkpoint inhibition in the treatment of ovarian cancer. [2022]

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

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. [2022]

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

Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. [2022]