Nivolumab +/- Ipilimumab for Ovarian Cancer

Not currently recruiting at 3 trial locations

Overseen By Roxanne Wood, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Don Dizon

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Brain metastases, Autoimmune disease, 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: 12

Duration: Varies by arm (2-6 weeks per cycle)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two drugs, Nivolumab (Opdivo) and Ipilimumab (Yervoy), in treating recurrent or metastatic ovarian cancer, specifically clear cell carcinoma. The researchers aim to determine if these drugs can enhance the immune system's ability to fight the cancer. The trial includes different groups, with some receiving only one drug and others receiving both. Individuals with clear cell carcinoma of the ovary, fallopian tube, or primary peritoneal origin who have undergone at least one round of chemotherapy may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop any chemotherapy or radiotherapy at least 4 weeks before starting, and endocrine therapy must be stopped 7 days prior. If you are on systemic corticosteroids or other immunosuppressive medications, you need to stop them 14 days before starting the trial.

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

A previous study showed that Nivolumab had promising safety results for ovarian cancer patients. Research indicates that this treatment is generally well-tolerated. Some patients experienced mostly mild side effects, such as fatigue or skin reactions.

For the combination of Nivolumab and Ipilimumab, research also shows good safety outcomes. This combination led to a promising increase in survival. However, some patients experienced more serious side effects, such as vomiting and pneumonia, although these were not very common.

Both treatments have been used and studied in other types of cancer, which supports their safety. Joining a trial like this contributes to important research, while healthcare professionals closely monitor participants to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab and Ipilimumab for ovarian cancer because these treatments work by harnessing the body's immune system to fight cancer cells, a method known as immunotherapy. Unlike traditional treatments like chemotherapy, which directly target cancer cells but can also harm healthy cells, Nivolumab and Ipilimumab specifically target and block proteins that prevent the immune system from attacking cancer. This novel approach has the potential to enhance the body's natural defenses to recognize and destroy cancer cells more effectively. Additionally, while current treatments often focus on symptom management, these drugs aim to provide a more targeted attack on the cancer, potentially leading to better outcomes for patients.

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

Research has shown that nivolumab, one of the treatments in this trial, may effectively treat ovarian cancer. In one study, patients using nivolumab lived for an average of 20 months. In this trial, some participants will receive nivolumab alone, while others will receive a combination of nivolumab and ipilimumab. When combined with ipilimumab, the average survival time increased to 24.7 months, suggesting that using both drugs together can improve outcomes for ovarian cancer patients. Additionally, the combination treatment had a better response rate than nivolumab alone. These findings indicate that nivolumab, either by itself or with ipilimumab, could be a promising treatment for ovarian cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Don Dizon, MD

Principal Investigator

Brown University Oncology Research Group (BrUOG) & Lifespan Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with clear cell carcinoma of ovarian, fallopian tube, primary peritoneal, or extra-renal origin who have progressed after prior treatments. They must have good organ function and performance status, no history of certain immune diseases or severe allergies to monoclonal antibodies, not be pregnant or breastfeeding, and agree to use effective contraception.

Inclusion Criteria

My ovarian, fallopian, or peritoneal cancer worsened after platinum and taxane treatment.

My clear cell cancer has worsened after at least one treatment for its advanced stage.

leukocytes ≥3,000/mcL

Exclusion Criteria

You have had a serious allergic reaction to any type of medication called monoclonal antibodies.

I haven't taken high-dose steroids or other immune-weakening drugs in the last 14 days.

I have previously received treatments targeting the immune system for cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab 240 mg every 2 weeks or Nivolumab 240 mg with Ipilimumab 1mg/kg every 6 weeks

Varies by arm (2-6 weeks per cycle)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The study is testing the effectiveness of Nivolumab alone or in combination with Ipilimumab in treating clear cell carcinomas. These drugs are designed to help the immune system recognize and attack cancer cells by blocking pathways that cancer uses to hide from immune cells.

How Is the Trial Designed?

Group I: Arm 2 Nivolumab and Ipilimumab Ovarian Experimental Treatment 2 Interventions

Nivolumab 240 mg every 2 weeks Ipilimumab 1mg/kg day 1 Cycle=6 weeks

Group II: Arm 2 Nivolumab and Ipilimumab Extra-renal Experimental Treatment 2 Interventions

Nivolumab 240 mg every 2 weeks Ipilimumab 1mg/kg day 1 Cycle=6 weeks

Group III: Arm 1 Nivolumab Ovarian Experimental Treatment 1 Intervention

Nivolumab 240 mg Day 1 Cycle = 2 weeks

Group IV: Arm 1 Nivolumab Extra-renal Experimental Treatment 1 Intervention

Nivolumab 240 mg Day 1 Cycle = 2 weeks

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?

Don Dizon

Lead Sponsor

Trials

3

Recruited

50+

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

The Miriam Hospital

Collaborator

Trials

252

Recruited

39,200+

Women and Infants Hospital of Rhode Island

Collaborator

Trials

119

Recruited

59,200+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Rhode Island Hospital

Collaborator

Trials

275

Recruited

71,400+

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]

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]

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]

Intra-tumoral immune cell density is a significant prognostic factor in epithelial ovarian cancer, suggesting that the immune environment plays a crucial role in disease outcomes.

Despite the rationale for using PD1/PD-L1 inhibitors in treating relapsed ovarian cancer, clinical trials have not shown promising results, leading to the exploration of combination therapies and earlier intervention strategies to improve efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in ovarian cancer: where do we stand? Leary, A., Tan, D., Ledermann, J.[2021]

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]

The combination of the FRα vaccine TPIV200 and the PD-L1 inhibitor durvalumab was well tolerated in 27 patients with advanced platinum-resistant ovarian cancer, showing a low grade 3 toxicity rate of 18.5%.

While the overall response rate was low (3.7% partial response and 33.3% stable disease), the median overall survival was notably long at 21 months, suggesting potential benefits from this immunotherapy approach in a heavily pretreated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial. Zamarin, D., Walderich, S., Holland, A., et al.[2021]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

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]

Citations

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

Randomized Phase II Trial of Nivolumab Versus ... In conclusion, the combination of nivolumab and ipilimumab induction followed by nivolumab maintenance in ovarian cancer resulted in superior response rate and ...

2. 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 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA5500

Final results of BrUOG 354: A randomized phase II trial ... Conclusions: Immunotherapy demonstrated important, meaningful, and durable activity in people with previously treated gynecologic CCC including ...

4. cancernetwork.com cancernetwork.com/view/nivolumab-ipilimumab-improves-responses-in-ovarian-gyn-clear-cell-carcinoma

Nivolumab/Ipilimumab Improves Responses in Ovarian ... The median overall survival (OS) was 24.7 months (95% CI, 5.9-not reached) vs 17.3 months (95% CI, 2.1-42.7). “Immunotherapy represents an ...

5. onclive.com onclive.com/view/com701-plus-bms-986207-nivolumab-shows-early-activity-in-platinum-resistant-ovarian-cancer

COM701 Plus BMS-986207/Nivolumab Shows Early ... Of those who responded to treatment, 20% had a partial response, 25% achieved stable disease, and 55% experienced disease progression. The ...

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. cancernetwork.com cancernetwork.com/view/nivolumab-meets-orr-pfs24-end-points-in-dmmr-uterine-and-ovarian-cancer

Nivolumab Meets ORR/PFS24 End Points in dMMR ... The ORR was 58.8% (97.5% CI, 40.7%-100%), and the PFS24 rate was 64.7% (97.5% CI, 46.5%-100%). The median follow-up was 42.1 months, and the ...

9. 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 ...