Etigilimab + Nivolumab for Ovarian Cancer

Overseen by Shannon Westin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disorders, Active infection, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, etigilimab and nivolumab, to help patients with certain types of cancer that don't respond to standard treatments. The drugs work by boosting the immune system's ability to attack cancer cells.

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 cannot be on any concurrent cancer treatments, and there may be a required washout period (time without taking certain medications) for some treatments before starting the trial.

What data supports the effectiveness of the drug Etigilimab + Nivolumab for ovarian cancer?

Research shows that immune checkpoint inhibitors, like Nivolumab, are being explored for ovarian cancer due to the cancer's ability to evade the immune system. However, single-agent PD-1 inhibitors have shown limited success, suggesting that combining them with other treatments, like Etigilimab, might enhance their effectiveness. ^{1 2 3 4 5}

Is the combination of Etigilimab and Nivolumab safe for humans?

Nivolumab, when used with other drugs like ipilimumab, has shown a manageable safety profile in treating conditions like non-small cell lung cancer, but it can cause immune-related side effects. It's important to monitor for these side effects and manage them early. ^{1 2 5 6 7}

How is the drug Etigilimab + Nivolumab unique for ovarian cancer?

Etigilimab + Nivolumab is unique because it combines two immune checkpoint inhibitors, potentially enhancing the immune system's ability to fight ovarian cancer, which has shown limited response to single-agent treatments. This combination aims to improve efficacy by targeting different pathways in the immune response. ^{1 3 5 8 9}

Research Team

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with recurrent clear cell ovarian, peritoneal, or fallopian tube cancer that hasn't responded to platinum-based therapy. Participants must have good organ function and no major unresolved health issues. They can't have had recent cancer treatments, use immunosuppressive drugs, or have certain medical conditions that could affect the study's results.

Inclusion Criteria

My cancer is a recurrent clear cell type in the ovary, peritoneum, or fallopian tube.

I do not have brain cancer or cancer spread to my brain or its coverings.

Ability to provide signed informed consent

Exclusion Criteria

I do not have active infections like TB, hepatitis B, C, or HIV.

I have not taken immunosuppressive medication in the last 14 days.

I don't have lasting side effects from cancer treatment, except for hair loss or skin changes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive etigilimab and nivolumab on Days 1 and 15 of each study cycle. In Cycle 1, etigilimab is administered on Day 1 and nivolumab on Day 2. From Cycle 2 onwards, both drugs are administered on Day 1.

6 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Etigilimab (Checkpoint Inhibitor)
• Nivolumab (Checkpoint Inhibitor)

Trial Overview The study tests if etigilimab combined with nivolumab can control advanced ovarian cancers resistant to standard treatments. It's a single-arm phase II trial where all participants receive both drugs to see how effective this combination is.

Participant Groups

Group I: Etigilimab plus Nivolumab Experimental Treatment 2 Interventions

Participants will receive the study drugs on Days 1 and 15 of each study cycle,Cycle 1, Participants will receive the drugs on separate days (etigilimab on Day 1 and nivolumab on Day 2). Starting with Cycle 2, you will receive both drugs on Day 1 (separated by 2 hours).

Nivolumab is already approved in Canada, Switzerland for the following indications:

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+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

Mereo BioPharma

Industry Sponsor

Trials

23

Recruited

1,700+

Findings from Research

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]

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 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]

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]

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 the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., 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]

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 2 study involving 38 women with relapsed epithelial ovarian cancer, the combination of nivolumab and bevacizumab showed an objective response rate of 28.9%, indicating potential efficacy, especially in patients with platinum-sensitive disease (40.0% response rate).

Most participants (89.5%) experienced treatment-related adverse events, with 23.7% having severe (grade 3 or higher) events, highlighting the need for careful monitoring of safety in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial. Liu, JF., Herold, C., Gray, KP., et al.[2021]

References

1. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in ovarian cancer: where do we stand? [2021]

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

6. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

7. 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]

8. England 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. [2021]

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

Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial. [2021]