Nivolumab + BMS-986205 for Endometrial Cancer

Not currently recruiting at 9 trial locations

Overseen By Vicky Makker, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, IDO inhibitors

Disqualifiers: Autoimmune disease, Immunodeficiency, Uncontrolled illness, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining nivolumab, a treatment already used for some cancers, with an experimental drug called BMS-986205, is more effective at treating endometrial cancer than nivolumab alone. Researchers hope the combination treatment might shrink the cancer or prevent its recurrence, though side effects may occur. The trial seeks women with diagnosed endometrial cancer that has returned or persists despite prior treatment and who have measurable tumors. 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 protocol does not specify whether you must stop taking your current medications. However, you cannot use immunosuppressive medications within 28 days before starting the trial, except for certain low-dose corticosteroids. It's best to discuss your specific medications with the trial team.

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

Research has shown that using nivolumab with BMS-986205 is generally safe for people with endometrial cancer. In one study, patients tolerated nivolumab alone and with BMS-986205 well, with most not experiencing severe side effects. Another study determined that the highest safe dose of BMS-986205 with nivolumab was 200 mg; however, this trial uses a lower dose of 100 mg for added caution. Overall, past research suggests these treatments are safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for endometrial cancer, which typically involve surgery, chemotherapy, and radiation, Nivolumab alone and in combination with BMS-986205 offer a novel approach. Nivolumab is an immunotherapy drug that works by blocking the PD-1 protein on immune cells, effectively helping the body's immune system to better detect and fight cancer cells. When combined with BMS-986205, an IDO-inhibitor, this treatment targets enzymes that suppress the immune system, potentially enhancing the immune response against cancer. Researchers are excited about these treatments because they represent a shift from traditional therapies, focusing on harnessing the body's own defenses to combat the cancer more effectively.

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

In this trial, participants will receive either nivolumab alone or with the experimental drug BMS-986205. Research suggests that combining nivolumab with BMS-986205 might help treat endometrial cancer. In one study, this combination reduced tumor size in 8.3% of patients, while nivolumab alone did not show any tumor reduction. The combination is believed to enhance the immune system's ability to fight cancer cells. Although there is potential, the response rate indicates that not every patient will benefit, and further research is needed to fully understand its effectiveness. ^{2 6 7 8 9}

Who Is on the Research Team?

Chrisann Kyi, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with certain types of persistent or recurrent endometrial cancer, including carcinosarcoma. They must have had one prior platinum-based chemotherapy and can't be pregnant or breastfeeding. Participants need measurable disease by specific criteria, adequate organ function, and a life expectancy of at least 12 weeks.

Inclusion Criteria

I have had one platinum-based chemotherapy for endometrial cancer.

I am fully active or can carry out light work.

My condition is recurrent or persistent endometrial cancer or carcinosarcoma.

Exclusion Criteria

I experience seizures that my medication cannot control.

History of hypersensitivity to nivolumab

You have received an organ transplant from another person in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab 480 mg every 4 weeks, with or without BMS-986205 100 mg

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986205
• Nivolumab

Trial Overview The study compares the effects of nivolumab alone to nivolumab combined with an experimental drug called BMS-986205 in treating endometrial cancer that hasn't responded to previous treatments. The goal is to see if adding BMS-986205 improves outcomes.

How Is the Trial Designed?

Group I: Nivolumab with IDO-inhibitor, BMS- 986205 Experimental Treatment 2 Interventions

Nivolumab 480 mg every 4 weeks with BMS-986205 100 mg.

Group II: Nivolumab alone Experimental Treatment 1 Intervention

Nivolumab 480 mg every 4 weeks.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union 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 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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of PD-1 Checkpoint Inhibition in Gynecologic Malignancies. Garcia, C., Ring, KL.[2022]

Pembrolizumab, an anti-PD-1 antibody, shows promise as a treatment for recurrent endometrial cancer, particularly due to the cancer's high rates of microsatellite instability and mismatch repair deficiency.

In a rare case, a patient achieved long-term complete remission from recurrent endometrial cancer after experiencing severe immune-related adverse events (irAEs), specifically colitis, following pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of recurrent endometrial cancer with long-term complete remission following pembrolizumab-induced severe immune-related adverse event colitis. Yamamoto, A., Nagashima, T., Imai, Y., et al.[2022]

The combination of lenvatinib and pembrolizumab significantly improved treatment outcomes for patients with advanced endometrial cancer compared to chemotherapy, regardless of tumor characteristics, based on data from Study-309/KEYNOTE-775.

Common adverse reactions included hypothyroidism, hypertension, and fatigue, with effective management strategies involving patient education, monitoring, and appropriate dose adjustments to minimize treatment interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab. Colombo, N., Lorusso, D., Monk, BJ., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved for treating relapsed MSI-H endometrial cancer after chemotherapy, showing promise in restoring anti-tumor immunity by blocking PD-1 interactions.

Despite encouraging response rates in MSI-H patients, over 50% do not respond to pembrolizumab, highlighting the need for better understanding of MSI status and identifying specific patient populations that may benefit from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. Turinetto, M., Lombardo, V., Pisano, C., et al.[2022]

A patient with stage IV endometrial cancer, who was MMR-proficient and PD-L1-negative, showed a strong and lasting response to a combination of PD-1 and CTLA-4 inhibitors, nivolumab and ipilimumab, for over 12 months.

This case suggests that there may be an endometrial cancer subtype that responds to immune checkpoint inhibitors through mechanisms not solely related to MMR deficiency or PD-L1 positivity, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep and Durable Response With Combination CTLA-4 and PD-1 Blockade in Mismatch Repair (MMR)-proficient Endometrial Cancer. Oh, MS., Chae, YK.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

The phase III RUBY and NRG-GY018 trials demonstrated that women with newly diagnosed or first-recurrent advanced endometrial cancer benefit from combining a PD-1 inhibitor (dostarlimab or pembrolizumab) with standard chemotherapy.

This combination treatment significantly prolonged progression-free survival, and there was a positive trend in overall survival, indicating its potential effectiveness in managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ICI-Chemo New Standard for Endometrial Cancer. [2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.5589

A phase II trial of IDO-inhibitor, BMS-986205 (IDO), and PD ... NIVO in combination with IDO showed ORR of 8.3%. No responses were observed with NIVO monotherapy. The trial closed to accrual due to lack of ...

2. clinicaltrial.be clinicaltrial.be/en/details/4698?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&only_active=0&only_eligible=0&only_recruiting=0&per_page=20

Study of BMS-986205 and Nivolumab in Endometrial ... This study will compare the effects of treatment with nivolumab alone versus those of nivolumab plus the experimental drug BMS-986205.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04007588

NCT04007588 | A Phase II Trial of Neoadjuvant Treatment ... Nivolumab, Ipilimumab, and BMS-986205 work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10891185/

Phase I/II trial of BMS-986205 and nivolumab as first line ... Combination BMS-986,205 and nivolumab showed a manageable safety profile with durable benefit as first-line therapy in a meaningful subset of ...

5. researchgate.net researchgate.net/publication/361120315_A_phase_II_trial_of_IDO-inhibitor_BMS-986205_IDO_and_PD-1_inhibitor_nivolumab_NIVO_in_recurrent_or_persistent_endometrial_cancer_EC_CA017-056

A phase II trial of IDO-inhibitor, BMS-986205 (IDO), and PD ... A phase II trial of IDO-inhibitor, BMS-986205 (IDO), and PD-1 inhibitor, nivolumab (NIVO), in recurrent or persistent endometrial cancer (EC; CA017-056).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04106414

Study of BMS-986205 and Nivolumab in Endometrial ... This study will compare the effects of treatment with nivolumab alone versus those of nivolumab plus the experimental drug BMS-986205. Adding BMS-986208 to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8207707/

Immunotherapy in endometrial cancer: rationale, practice and ... Combination of IDO1 inhibitor (such as BMS-986205) with ICBs might be an alternative strategy for EC patients. The combination of nivolumab with ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04106414?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(bms%20986205)))&rank=9

Study of BMS-986205 and Nivolumab in Endometrial ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

9. news.bms.com news.bms.com/news/details/2017/Encouraging-Response-Observed-with-Opdivo-nivolumab-Plus-Investigational-IDO1-Inhibitor-BMS-986205-in-Heavily-Pre-Treated-Patients-with-Advanced-Cancers-in-Phase-12a-Study-CA017-003/default.aspx

Encouraging Response Observed with Opdivo (nivolumab) ... In the dose escalation phase, the maximum tolerated dose (primary endpoint) of BMS-986205 in combination with Opdivo was 200 mg. Based on safety ...