Nivolumab +/− Ipilimumab for Ovarian Cancer

No longer recruiting at 240 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two immunotherapy drugs, nivolumab (Opdivo) and ipilimumab (Yervoy), to determine if they can help the immune system combat ovarian cancer that has persisted after earlier treatment or returned. These drugs aim to enhance the body's natural defenses to target and potentially shrink tumors. Participants may receive either nivolumab alone or the combination of nivolumab and ipilimumab. Individuals with ovarian, fallopian tube, or primary peritoneal cancer that hasn't responded to previous treatments or has returned might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

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.

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

Research shows that combining nivolumab and ipilimumab is generally safe for patients. Studies have found that this combination has a good safety record and offers significant health benefits. Common side effects include vomiting and pneumonia, but these occur in only a small number of patients.

Nivolumab alone has also been tested and is considered safe for treating ovarian cancer. Earlier trials showed positive results with manageable side effects. Patients treated with nivolumab had an average survival time of 20 months.

Both treatments have received FDA approval for other uses, supporting their safety in humans. However, like any treatment, there is a risk of side effects. Clinical trial participants are closely monitored to manage any negative effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Nivolumab and ipilimumab are exciting treatments for ovarian cancer because they represent a different approach than the traditional chemotherapy options. Unlike chemotherapy, which directly targets rapidly dividing cells, nivolumab and ipilimumab are immunotherapy drugs that help the immune system recognize and attack cancer cells. Nivolumab is a PD-1 inhibitor, while ipilimumab targets CTLA-4, both of which are proteins that can help cancer cells evade the immune system. This dual-action approach has the potential to enhance the body’s natural defenses and improve outcomes for patients with ovarian cancer. Researchers are particularly hopeful that these treatments could lead to longer-lasting responses and potentially fewer side effects compared to standard treatments.

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

In this trial, participants will receive either nivolumab alone or a combination of nivolumab and ipilimumab. Research has shown that using nivolumab and ipilimumab together can be effective for some cancers. One study found that people who received both drugs lived for an average of 24.7 months, compared to 17.3 months for those who only received nivolumab. The combination also resulted in a 36% response rate, meaning more patients saw their tumors shrink. This suggests that the two drugs together might be more effective than nivolumab alone because they enhance the immune system's ability to fight cancer cells. These results are promising for treating stubborn or recurring ovarian, primary peritoneal, and fallopian tube cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Dimitry Zamarin

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. onclive.com onclive.com/view/nivolumab-ipilimumab-yields-responses-in-ovarian-clear-cell-carcinoma

Nivolumab/Ipilimumab Yields Responses in Ovarian Clear ... The median overall survival was 17.3 months with nivolumab and 24.7 months with the combination. Importantly, people who responded to the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8593709/

Combination immunotherapy with nivolumab and ... Overall, our trial demonstrates significant clinical efficacy of nivolumab and ipilimumab combination immunotherapy with a favorable safety ...

3. ono-pharma.com ono-pharma.com/sites/default/files/en/news/press/sm_cn161207.pdf

Opdivo (nivolumab) Alone or Combined With Yervoy ( ... Grade 3/4 treatment-related discontinuation rates were 10% in the Opdivo plus Yervoy group and 4% in the Opdivo group. Bristol-Myers Squibb (BMS) ...

4. targetedonc.com targetedonc.com/view/nivolumab-plus-ipilimumab-improves-os-and-response-in-frontline-uhcc

Nivolumab Plus Ipilimumab Improves OS and Response in ... Nivolumab with ipilimumab also demonstrated a significantly higher overall response rate (ORR) at 36% compared with the lenvatinib/sorafenib ...

5. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Announces-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Significantly-Improved-Overall-Survival-Compared-to-Lenvatinib-or-Sorafenib-as-First-Line-Treatment-for-Patients-with-Advanced-Hepatocellular-Carcinoma-in-CheckMate--9DW-Trial/default.aspx

Bristol Myers Squibb Announces Opdivo (nivolumab) Plus ... Opdivo plus Yervoy demonstrated a significantly reduced risk of symptom deterioration of 24% compared to lenvatinib or sorafenib (HR: 0.76, 95% ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2015.62.3397

Safety and Antitumor Activity of Anti–PD-1 Antibody, ... The median progression-free survival time was 3.5 months (95% CI, 1.7 to 3.9 months), and the median overall survival time was 20.0 months (95% CI, 7.0 months ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26351349/

Safety and Antitumor Activity of Anti-PD-1 Antibody, ... The median progression-free survival time was 3.5 months (95% CI, 1.7 to 3.9 months), and the median overall survival time was 20.0 months (95% CI, 7.0 months ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7255977/

Randomized Phase II Trial of Nivolumab Versus ... The median progression-free survival (PFS) was 2 and 3.9 months in the nivolumab and nivolumab plus ipilimumab groups, respectively, with a PFI-stratified ...

9. ocrahope.org ocrahope.org/news/small-trial-shows-promising-results-for-nivolumab-in-ovarian-cancer/

Small Trial Shows Promising Results for Nivolumab in ... The median progression-free survival time was 3.5 months and the median overall survival time was 20 months. Results of the clinical trial are ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT04024878

NeoVax With Nivolumab in Patients With Ovarian Cancer To demonstrate that regimen of NeoVax with Nivolumab is feasible and safe for the treatment of patients with ovarian cancer. Safety analysis will be performed ...