Retifanlimab Combination Therapy for Endometrial Cancer

(POD1UM-204 Trial)

Recruiting at 103 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

206 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing retifanlimab, an immunotherapy drug, in patients with advanced endometrial cancer that has not improved with standard chemotherapy. The drug helps the immune system better identify and destroy cancer cells. It can be used alone or with other treatments.

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.

What data supports the effectiveness of the drug combination Retifanlimab and Pemigatinib for endometrial cancer?

Research shows that combining a PD-1 inhibitor, like Retifanlimab, with chemotherapy can help women with advanced endometrial cancer live longer without the disease getting worse. Similar drugs, such as pembrolizumab, have shown benefits in prolonging progression-free survival in endometrial cancer. ^{1 2 3 4 5}

What safety data exists for Retifanlimab Combination Therapy for Endometrial Cancer?

The safety profile of lenvatinib plus pembrolizumab, a similar combination therapy, includes common side effects like fatigue, high blood pressure, and digestive issues, which were generally manageable with supportive care. Serious side effects led to treatment discontinuation in about 21% of patients, but early identification and intervention helped manage these effects. ^{3 6 7 8 9}

What makes Retifanlimab unique for treating endometrial cancer?

Retifanlimab is a PD-1 inhibitor, similar to other drugs like dostarlimab and pembrolizumab, which are used in combination with chemotherapy to improve outcomes in advanced endometrial cancer. Its uniqueness may lie in its specific formulation or combination with other therapies, although the exact differences are not detailed in the available research. ^{1 3 10 11 12}

Research Team

Mark Cornfield

Principal Investigator

Incyte Corporation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial. [2022]

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

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. [2022]

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

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

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

Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: a gynecologic oncology group study. [2022]

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

Characterization and Management of Adverse Reactions in Patients with Advanced Endometrial Carcinoma Treated with Lenvatinib Plus Pembrolizumab. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab. [2023]

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

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. [2023]

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

Emerging Treatment Options for Advanced or Recurrent Endometrial Cancer. [2022]

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

Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study. [2023]

11. England 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. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Management of Metastatic Endometrial Cancer: Physicians' Choices Beyond the First Line. A MITO Survey. [2022]