Pembrolizumab + Epacadostat for Kidney Cancer

No longer recruiting at 172 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must not be taking: Investigational treatments

Disqualifiers: Autoimmune, CNS metastases, cardiac, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Minimum up to 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the combination of pembrolizumab and epacadostat (an IDO inhibitor) is more effective and safe than the usual treatments, sunitinib or pazopanib, for kidney cancer that has spread or cannot be surgically removed. It targets individuals with renal cell carcinoma with a clear cell component who have not tried other treatments. Suitable candidates are those diagnosed with this type of kidney cancer and have not received any previous systemic therapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you must not have received any prior systemic therapy for your kidney cancer. It's best to discuss your current medications with the trial team.

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

Research has shown that earlier studies tested the combination of pembrolizumab and epacadostat for safety. The observed side effects matched those expected from previous tests.

Pembrolizumab, when used alone, is already approved for treating other types of cancer, which supports its safety profile. Epacadostat has also been tested with pembrolizumab in patients with various cancers, including kidney cancer. These studies found that patients generally tolerated the treatments well.

While side effects can occur, research suggests that this combination is as safe as expected from earlier tests. Participants should discuss potential risks with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for kidney cancer?

Researchers are excited about Pembrolizumab + Epacadostat for kidney cancer because this combination targets the immune system in a novel way. Unlike the standard treatments, sunitinib and pazopanib, which are tyrosine kinase inhibitors, Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. Epacadostat is an IDO1 inhibitor that works by reducing immune suppression in tumors. Together, they aim to enhance the body's natural ability to fight cancer more effectively than current options.

What evidence suggests that pembrolizumab plus epacadostat could be an effective treatment for kidney cancer?

This trial will evaluate the combination of pembrolizumab and epacadostat for treating kidney cancer. Research has shown that using pembrolizumab and epacadostat together is promising for treating advanced solid tumors. In earlier studies, this combination effectively shrank or controlled tumors. Patients generally tolerated the treatment well, and evidence of success exists in cancers like bladder cancer. These results suggest it might also work for kidney cancer, which is similar. Overall, this combination offers hope for people with advanced cancers. ^{2 4 6 7 8}

Who Is on the Research Team?

Mark Jones, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer (mRCC) who haven't had any previous systemic treatments. Participants should be relatively healthy, able to perform daily activities (70% on the Karnofsky scale), and have a tumor that can be measured. They must provide a tissue sample of their tumor and not have other active cancers or severe health issues like heart problems or autoimmune diseases.

Inclusion Criteria

You have a disease that can be measured using specific guidelines.

My kidney cancer is advanced or has spread, and tests show it's mostly clear-cell type.

I am mostly able to care for myself and carry out daily activities.

Exclusion Criteria

I am following or have followed the treatment plan as outlined in the study protocol.

Currently receiving or has received an investigational treatment as part of a study of an investigational agent or has used an investigational device within 4 weeks before randomization.

History of severe hypersensitivity reaction to study treatments or their excipients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab plus epacadostat or standard of care (sunitinib or pazopanib) for locally advanced/metastatic renal cell carcinoma

Minimum up to 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 months

What Are the Treatments Tested in This Trial?

Interventions

• Epacadostat
• Pembrolizumab

Trial Overview The study compares the effectiveness of combining Pembrolizumab (an immunotherapy drug) with Epacadostat versus standard treatments Sunitinib or Pazopanib in treating mRCC. The goal is to see if this new combination works better for patients who are newly diagnosed with metastatic kidney cancer.

How Is the Trial Designed?

Group I: Pembrolizumab + Epacadostat Experimental Treatment 2 Interventions

Group II: SoC (Sunitinib or Pazopanib) Active Control 2 Interventions

Standard of care (SoC) (sunitinib or pazopanib monotherapy).

Epacadostat is already approved in United States for the following indications:

Approved in United States as Epacadostat for:

• None approved; Orphan designation for stage IIB-IV melanoma

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an immune checkpoint inhibitor for non-small cell lung carcinoma, has been linked to adverse renal outcomes, including acute kidney injury.

In a reported case, a patient developed acute tubulointerstitial nephritis after starting pembrolizumab, and while renal function improved with long-term corticosteroid treatment after discontinuation of the drug, it only improved partially.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. Basnet, S., Dhital, R., Tharu, B.[2020]

This study presents the first known case of a patient with metastatic melanoma who was successfully treated with pembrolizumab while undergoing hemodialysis, highlighting its potential efficacy in patients with end-stage renal disease.

Pembrolizumab, an FDA-approved monoclonal antibody for metastatic melanoma and non-small cell lung cancer, shows promise for use in patients with renal complications, although specific dosing guidelines for such patients are still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. Chang, R., Shirai, K.[2019]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

In a phase 3 trial involving 706 patients with unresectable stage III or IV melanoma, the combination of epacadostat and pembrolizumab did not show any significant improvement in progression-free survival or overall survival compared to pembrolizumab alone.

The most common serious side effects were similar between the two groups, with no treatment-related deaths reported, indicating that the combination therapy was generally safe but ineffective in enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Long, GV., Dummer, R., Hamid, O., et al.[2020]

In a phase 3 trial with 861 patients suffering from advanced clear-cell renal-cell carcinoma, the combination of pembrolizumab and axitinib significantly improved overall survival (89.9% vs. 78.3% at 12 months) compared to sunitinib, with a hazard ratio for death of 0.53.

Patients receiving pembrolizumab plus axitinib also experienced longer progression-free survival (15.1 months vs. 11.1 months) and a higher objective response rate (59.3% vs. 35.7%), indicating that this combination therapy is more effective than sunitinib for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. Rini, BI., Plimack, ER., Stus, V., et al.[2022]

In a trial involving 62 patients with advanced solid tumors, the combination of epacadostat (an IDO1 inhibitor) and pembrolizumab (a PD-1 inhibitor) was generally well tolerated, with no maximum tolerated dose reached and only 11% of patients discontinuing due to treatment-related adverse events.

The combination therapy showed promising antitumor activity, with 55% of melanoma patients and responses observed in other cancer types, indicating potential effectiveness across various advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epacadostat Plus Pembrolizumab in Patients With Advanced Solid Tumors: Phase I Results From a Multicenter, Open-Label Phase I/II Trial (ECHO-202/KEYNOTE-037). Mitchell, TC., Hamid, O., Smith, DC., et al.[2023]

In a phase II study involving 110 patients with advanced clear cell renal cell carcinoma (ccRCC), pembrolizumab demonstrated a 36.4% objective response rate, indicating significant antitumor activity as a first-line treatment.

The treatment was generally well-tolerated, with 30% of patients experiencing grade 3-5 adverse events, primarily colitis and diarrhea, which aligns with safety profiles observed in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. McDermott, DF., Lee, JL., Bjarnason, GA., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11270760/

A randomized, open-label, phase 3 trial of pembrolizumab ... In a phase 1 study of patients with advanced solid tumors, the combination of pembrolizumab plus epacadostat has shown promising antitumor ...

2. actionkidneycancer.org actionkidneycancer.org/epacadostat-plus-pembrolizumab-combination-shows-promise-in-advanced-solid-tumours/

Epacadostat plus pembrolizumab combination shows ... The researchers conclude that epacadostat in combination with pembrolizumab offers promising anti-tumour activity with an acceptable safety profile in multiple ...

3. merck.com merck.com/news/updated-data-from-echo-202-trial-of-incytes-epacadostat-in-combination-with-mercks-keytruda-pembrolizumab-demonstrate-clinical-activity-across-multiple-tumor-types/

Updated Data from ECHO-202 Trial of Incyte's Epacadostat ... “The combination of KEYTRUDA and epacadostat as a treatment for multiple advanced solid tumors has shown promise in our preliminary Phase 1/2 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4645566/

Preliminary results from a Phase I/II study of epacadostat ... Epacadostat with pembrolizumab was generally well tolerated and efficacy data suggest promising clinical activity. Correlations between biomarker expression and ...

5. researchgate.net researchgate.net/publication/345682256_Epacadostat_plus_pembrolizumab_in_patients_with_advanced_RCC_Preliminary_phase_III_results_from_ECHO-202KEYNOTE-037

Preliminary phase I/II results from ECHO-202/KEYNOTE-037. This phase I/II study treating 444 patients with epacadostat and pembrolizumab found that this combination therapy was effective for urothelial carcinoma [76], ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02853344

NCT02853344 | Study of Pembrolizumab (MK-3475) ... The purpose of this study is to assess the safety and efficacy of monotherapy pembrolizumab (MK-3475) in participants with renal cell carcinoma (RCC).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6225502/

Epacadostat Plus Pembrolizumab in Patients With ... Tumors may evade immunosurveillance through upregulation of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. Epacadostat is a potent and highly selective IDO1 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02178722

NCT02178722 | Study to Explore the Safety, Tolerability ... The purpose of this study was to assess the safety, tolerability, and efficacy when combining MK-3475 and INCB024360 in participants with certain cancers. This ...