90 Participants Needed

Nivolumab +/− Ipilimumab for Endometrial Cancer

Recruiting at 88 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This phase II trial tests whether the combination of nivolumab and ipilimumab is better than nivolumab alone to shrink tumors in patients with deficient mismatch repair system (dMMR) endometrial carcinoma that has come back after a period of time during which the cancer could not be detected (recurrent). Deoxyribonucleic acid (DNA) mismatch repair (MMR) is a system for recognizing and repairing damaged DNA. In 2-3% of endometrial cancers this may be due to a hereditary condition resulted from gene mutation called Lynch Syndrome (previously called hereditary nonpolyposis colorectal cancer or HNPCC). MMR deficient cells usually have many DNA mutations. Tumors that have evidence of mismatch repair deficiency tend to be more sensitive to immunotherapy. There is some evidence that nivolumab with ipilimumab can shrink or stabilize cancers with deficient mismatch repair system. However, it is not known whether this will happen in endometrial cancer; therefore, this study is designed to answer that question. 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. Giving nivolumab in combination with ipilimumab may be better than nivolumab alone in treating dMMR recurrent endometrial carcinoma.

Will I have to stop taking my current medications?

The trial requires that any prior therapy directed at the tumor, including chemotherapy, targeted agents, biologic agents, immunologic agents, and investigational agents, must be stopped at least 4 weeks before joining the study. Hormonal therapy must be stopped at least 3 weeks before joining. If you are on chronic steroid therapy, you may need to adjust your dose to 10mg or less of prednisone or equivalent.

What data supports the effectiveness of the drug Nivolumab +/− Ipilimumab for Endometrial Cancer?

Research shows that drugs targeting the PD-1/PD-L1 pathway, like Nivolumab, have shown activity in endometrial cancer, especially in cases with specific genetic markers (mismatch repair deficiency). This suggests potential effectiveness for Nivolumab in treating endometrial cancer.12345

What safety information is available for the combination of Nivolumab and Ipilimumab?

The combination of Nivolumab and Ipilimumab can cause immune-related side effects in about half of the patients, such as diarrhea, liver inflammation, and lung issues. These side effects can be serious but are often reversible with proper management, including the use of steroids. Close monitoring by healthcare professionals is important to manage these side effects effectively.678910

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

The combination of Nivolumab and Ipilimumab is unique because it uses two immune checkpoint inhibitors that help the body's immune system recognize and attack cancer cells, which is different from traditional chemotherapy that directly targets and kills cancer cells.1112131415

Research Team

Dr. Haider Salih Mahdi, MD - Pittsburgh ...

Haider Mahdi, MD

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults over 18 with recurrent endometrial cancer that has a deficient mismatch repair system. Eligible participants may have had prior treatments but must be in good health with stable vital signs and organ function. Those with certain autoimmune diseases, severe allergies to the drugs being tested, or who are pregnant are excluded.

Inclusion Criteria

If you have rheumatoid arthritis, Sjogren's syndrome, or psoriasis, it should be controlled with topical medication. If you have certain antibodies in your blood, your doctor will check if your organs are affected before you can join the trial.
I have had 1 or 2 treatments for my condition before.
I have chronic hepatitis B but it's under control with treatment.
See 19 more

Exclusion Criteria

I am allergic to certain drugs similar to nivolumab or ipilimumab.
I have not had treatments targeting immune system checkpoints.
I stopped immunotherapy due to severe side effects.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab and ipilimumab or nivolumab alone, with cycles repeating every 3 weeks for up to 8 cycles, then every 4 weeks thereafter

24 weeks
8 visits (in-person) every 3 weeks, then monthly visits

Maintenance Therapy

Patients achieving complete response receive nivolumab for an additional 12 months

12 months
Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

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

Treatment Details

Interventions

  • Ipilimumab
  • Nivolumab
Trial OverviewThe study is testing if combining two immune system-boosting drugs, nivolumab and ipilimumab, can better shrink tumors compared to nivolumab alone in patients whose endometrial cancer has returned and shows DNA repair deficiencies.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (nivolumab and ipilimumab)Experimental Treatment5 Interventions
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle and ipilimumab IV over 90 minutes on day 1 of every other cycle. Cycles repeat every three weeks. Treatment with nivolumab and ipilimumab repeats for up to 8 cycles in the absence of disease progression, unacceptable toxicity, or CR. Patients then receive nivolumab alone on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression, unacceptable toxicity, or CR. MAINTENANCE THERAPY: Patients achieving CR receive nivolumab for an additional 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may optionally undergo collection of tissue samples on study as well as blood samples throughout the trial. Patients also undergo CT scan and/or MRI throughout the trial.
Group II: Arm II (nivolumab)Active Control4 Interventions
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for up to 8 cycles, then every 4 weeks thereafter in the absence of disease progression, unacceptable toxicity, or CR. MAINTENANCE THERAPY: Patients achieving CR receive nivolumab for an additional 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may optionally undergo collection of tissue samples on study as well as blood samples throughout the trial. Patients also undergo CT scan and/or MRI throughout the trial.

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

Find a Clinic Near You

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

In the KEYNOTE-158 study, pembrolizumab showed a clinically meaningful objective response rate in patients with advanced MSI-H/dMMR endometrial cancer, with 84 out of 90 patients completing health-related quality of life (HRQoL) assessments.
Patients receiving pembrolizumab experienced significant improvements in their quality of life, with mean scores on the QLQ-C30 and EQ-5D-3L questionnaires increasing notably, especially among those who achieved a complete or partial response to treatment.
Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study.O'Malley, DM., Bariani, GM., Cassier, PA., et al.[2022]
PD-1 and PD-L1 inhibitors have shown effectiveness in treating ovarian, endometrial, and cervical cancers, particularly in cases of mismatch repair-deficient endometrial cancers, which exhibit the highest response rates.
Testing for mismatch repair deficiency or high microsatellite instability is recommended for all women with progressive gynecologic cancers to determine eligibility for treatment with pembrolizumab, a PD-1 inhibitor.
The Role of PD-1 Checkpoint Inhibition in Gynecologic Malignancies.Garcia, C., Ring, KL.[2022]
Pembrolizumab and dostarlimab, immune checkpoint inhibitors, have been approved for treating advanced recurrent endometrial cancer in patients with specific molecular subgroups, particularly those with mismatch repair deficiency (MMRd) or microsatellite instability-high (MSI-H) status, based on data from 15 studies involving 1609 patients.
The combination of pembrolizumab or dostarlimab with lenvatinib has shown efficacy in patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) endometrial cancer, highlighting the importance of biomarker assessment to optimize treatment strategies for different molecular phenotypes.
Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 Pathway in Advanced, Recurrent Endometrial Cancer: A Scoping Review with SWOT Analysis.Johnson, RL., Ganesan, S., Thangavelu, A., et al.[2023]

References

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. [2022]
The Role of PD-1 Checkpoint Inhibition in Gynecologic Malignancies. [2022]
Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 Pathway in Advanced, Recurrent Endometrial Cancer: A Scoping Review with SWOT Analysis. [2023]
Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium. [2023]
Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer. [2023]
Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events. [2022]
Emerging options for the treatment of melanoma - focus on ipilimumab. [2020]
Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]
Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. [2022]
Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma. [2021]
Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]
Efficacy and safety of nivolumab with ipilimumab for recurrent malignant pleural mesothelioma after primary surgical intervention. [2023]
14.United Statespubmed.ncbi.nlm.nih.gov
Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial. [2022]
Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]