Retifanlimab Combination Therapy for Endometrial Cancer

(POD1UM-204 Trial)

Not currently recruiting at 114 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Incyte Corporation

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Carcinosarcoma, Sarcoma, Active autoimmune, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 4 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for advanced or metastatic endometrial cancer, particularly for those who haven't responded to platinum-based chemotherapy. Researchers are testing retifanlimab, an immunotherapy drug, alone or with other drugs to determine if these treatments can better manage the cancer. Participants will be grouped based on their previous treatments and specific cancer characteristics. The trial seeks women whose endometrial cancer has progressed despite past treatments and who have specific tumor features that can be tested. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you have not received anticancer therapy within 28 days before starting the study treatment, except for localized radiotherapy. If you are on chronic systemic steroids or have an active autoimmune disease requiring certain medications, you may need to stop or adjust those medications before participating.

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

Research has shown that retifanlimab is generally well tolerated, meaning most people can handle the treatment without severe side effects. In studies with patients who had a specific type of endometrial cancer (MSI-H/dMMR), retifanlimab demonstrated promising results in fighting tumors and was well received by patients.

For those considering the retifanlimab-epacadostat combination, direct safety information remains limited. However, similar treatments, such as lenvatinib with pembrolizumab, often cause side effects like tiredness and high blood pressure, which might provide an idea of what to expect.

The safety details for the retifanlimab-pemigatinib combination are also limited. As with other similar treatments, it is important to monitor for common side effects.

Lastly, the combination of retifanlimab with INCAGN02385 and INCAGN02390 is still under study, and specific safety information remains unclear. Since this is an early-phase study, researchers are closely monitoring and evaluating the treatment's safety.

Overall, while retifanlimab alone appears to be well tolerated, combinations might have different side effects. It is important to discuss any concerns with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about retifanlimab for endometrial cancer because, unlike traditional treatments like chemotherapy or radiation, it harnesses the power of the immune system. Retifanlimab is a checkpoint inhibitor that blocks proteins which cancer cells use to evade immune detection, helping the body naturally fight the cancer. Additionally, some trial arms combine retifanlimab with other innovative agents like epacadostat, an IDO1 inhibitor, and pemigatinib, an FGFR inhibitor. These combinations aim to enhance the immune response and target specific cancer pathways, offering potentially more effective and personalized treatment options.

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

Research has shown that retifanlimab, which participants in this trial may receive, has promising effects against tumors in patients with advanced endometrial cancer, especially those with genetic traits like MSI-H/dMMR. Previous studies found it generally well tolerated, with patients experiencing significant benefits.

In this trial, some participants will receive retifanlimab combined with epacadostat. This combination targets cancer cells more effectively by blocking pathways that help tumors grow and has shown potential for longer-lasting responses in cancer treatment.

Another group in this trial will receive the combination of retifanlimab and pemigatinib, which significantly extended the time patients lived without their cancer worsening. There is also a positive trend toward improving overall survival rates.

For the combination of retifanlimab with INCAGN02385 and INCAGN02390, early studies are examining its safety and effectiveness. This mix aims to boost the immune system's ability to fight cancer by targeting multiple pathways. ^{1 2 4 6 7}

Who Is on the Research Team?

Mark Cornfield

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

This trial is for women over 18 with advanced or metastatic endometrial cancer that worsened after platinum-based chemotherapy. They must have a good performance status, measurable tumor lesions, and specific genetic markers depending on the group they're assigned to. They can't join if they've had certain recent treatments, unresolved toxicity from past therapies, active hepatitis B or C, live vaccines recently, some immune conditions, known HIV with exceptions, CNS metastases or treatable disease.

Inclusion Criteria

My tumor is MMR deficient or has a POLE mutation.

My cancer has grown despite previous PD-1 or PD-L1 therapy and my tumor is MSI-H.

My tumor is MSI-High.

Exclusion Criteria

I have not received a live vaccine in the last 28 days.

My side effects from previous treatments have mostly gone away.

I am taking high doses of steroids or other drugs for an autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive retifanlimab alone or in combination with other therapies for advanced or metastatic endometrial cancer

up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pemigatinib
• Retifanlimab

Trial Overview The study tests retifanlimab alone or combined with other immunotherapies/targeted agents in patients whose endometrial cancer has progressed post-platinum chemotherapy. It's an open-label Phase 2 trial where everyone knows what treatment they're getting; it's not randomized.

How Is the Trial Designed?

Group I: Group F - retifanlimab + INCAGN02385 and INCAGN02390 Experimental Treatment 2 Interventions

Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab in combination with INCAGN02385 and INCAGN02390 intravenously

Group II: Group E - retifanlimab + epacadostat Experimental Treatment 2 Interventions

Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat

Group III: Group D - retifanlimab + pemigatinib Experimental Treatment 2 Interventions

Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral pemigatininb (FGFR 1,2,3 inhibitor)

Group IV: Group C - retifanlimab + epacadostat Experimental Treatment 2 Interventions

Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat (IDO1 inhibitor)

Group V: Group B - retifanlimab Experimental Treatment 1 Intervention

Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously

Group VI: Group A - retifanlimab Experimental Treatment 1 Intervention

Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously

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

Approved in United States as Zynyz for:

• Merkel cell carcinoma

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

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Published Research Related to This Trial

Dostarlimab demonstrated superior overall survival (OS) compared to doxorubicin in patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) advanced/recurrent endometrial cancer, with median OS not reached for dostarlimab versus 11.2 months for doxorubicin.

Dostarlimab also showed a better safety profile, with lower rates of grade ≥3 adverse events (48.1% for dostarlimab vs 78.3% for doxorubicin), indicating it may be a safer option for patients following platinum-based therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Indirect Comparison of the Efficacy and Safety of Dostarlimab and Doxorubicin for the Treatment of Advanced and Recurrent Endometrial Cancer. Mathews, C., Lorusso, D., Coleman, RL., et al.[2023]

In a study of 48 patients with recurrent endometrial cancer treated with pembrolizumab and lenvatinib, the best objective response rate was 23.8%, indicating a lower effectiveness compared to clinical trial results.

The treatment was associated with notable side effects, with 56.2% of patients requiring a dose reduction of lenvatinib and 16.7% discontinuing treatment due to adverse events, highlighting the importance of monitoring for safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. Kim, J., Noh, JJ., Lee, TK., 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]

In a study of 43 patients with recurrent endometrial cancer treated with lenvatinib and pembrolizumab, 84% experienced significant adverse events (AEs), with hypertension and weight loss being the most common.

Patients starting on a reduced dose of lenvatinib (10 mg or 14 mg) had significantly longer progression-free survival compared to those on the standard dose (20 mg), suggesting that dose optimization may improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. Zammarrelli, WA., Ma, W., Espino, K., et al.[2023]

A survey of oncologists in Italy revealed that while there is a good understanding of new treatments for endometrial cancer (EC), such as dostarlimab for MSI high patients, these innovations are not fully integrated into clinical practice, with only 13.3% performing all necessary molecular tests.

After the approval of dostarlimab, 75.6% of clinicians preferred it for second-line treatment in MSI high advanced EC patients, indicating a significant shift in treatment choice, while 77.8% plan to use lenvatinib plus pembrolizumab for MSS patients once approved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Metastatic Endometrial Cancer: Physicians' Choices Beyond the First Line. A MITO Survey. Giannone, G., Castaldo, D., Tuninetti, V., et al.[2022]

Patients with metastatic or recurrent endometrial cancer have a poor prognosis, but local recurrences may be treated effectively with radiation, especially when combined with chemotherapy.

Chemotherapy regimens using anthracyclines, platinum compounds, and paclitaxel show response rates over 20%, but while combination therapies yield higher response rates, they are also more toxic and have limited impact on overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy for advanced or recurrent endometrial carcinoma. Fleming, GF.[2019]

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]

The combination of lenvatinib and pembrolizumab is effective for treating advanced endometrial carcinoma, particularly in patients who have not responded to prior therapies, with manageable safety profiles similar to each drug used alone.

Common adverse reactions include hypothyroidism (51% incidence), fatigue, hypertension, and nausea, which typically occur within the first 10 weeks of treatment and can be effectively managed with dose adjustments and supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions in Patients with Advanced Endometrial Carcinoma Treated with Lenvatinib Plus Pembrolizumab. Makker, V., Taylor, MH., Oaknin, A., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38824752/

Antitumor activity and safety of the PD-1 inhibitor ... Retifanlimab was generally well tolerated and demonstrated encouraging anti-tumor activity in patients with pre-treated recurrent MSI-H/dMMR endometrial cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04463771

Study Details | NCT04463771 | Safety and Efficacy of ... This is a multicenter, open-label, nonrandomized, Phase 2 umbrella study of retifanlimab in participants who have advanced or metastatic endometrial cancer ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0090825824002464

Antitumor activity and safety of the PD-1 inhibitor ... Retifanlimab was generally well tolerated and demonstrated encouraging anti-tumor activity in patients with pre-treated recurrent MSI-H/dMMR endometrial cancer.

4. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-positive-results-phase-3-trial-evaluating

Incyte Announces Positive Results from Phase 3 Trial ... Patients in the retifanlimab and chemotherapy combination treatment group achieved a median overall survival (OS) of 18.1 months compared to ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02771-0/fulltext

755P Retifanlimab in patients with recurrent microsatellite ... Conclusions. Retifanlimab has shown notable clinical activity in previously treated MSI-H or dMMR endometrial cancer, which is consistent with other checkpoint ...

6. incytemi.com incytemi.com/document/Product%20Resources/Retifanlimab%20SCAC%20Prescribing%20Information%20(May%202025).pdf

ZYNYZ® (retifanlimab-dlwr) Indication and Usage. • ZYNYZ is a programmed death receptor-1 (PD-1)-blocking antibody indicated: — Squamous Cell Carcinoma of the Anal Canal (SCAC).

7. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incytes-retifanlimab-zynyzr-extends-progression-free-survival

Incyte's Retifanlimab (Zynyz®) Extends Progression-Free ... The positive efficacy and safety data presented today at ESMO illustrate the potential of retifanlimab in combination with carboplatin and ...