Favezelimab + Pembrolizumab for Endometrial Cancer

Recruiting at 46 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Antihypertensives

Disqualifiers: Organ transplant, Cardiovascular disease, 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

Compensation: Varies

Number of Visits: 17

160 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate pathologic complete response (pCR) rate of coformulated favezelimab/pembrolizumab (MK-4280A) or pembrolizumab as assessed by blinded central pathology review (BICR) in participants with cutaneous squamous cell carcinoma (cSCC) \[Cohort A\] and to evaluate lenvatinib in combination with coformulated favezelimab/pembrolizumab or pembrolizumab with respect to objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator in participants proficient in mismatch repair (pMMR) endometrial cancer (EC) \[Cohort B\].

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have adequately controlled blood pressure without antihypertensive medication and meet other health criteria. It's best to discuss your current medications with the trial team.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants must have adequately controlled blood pressure without antihypertensive medication and well-controlled HIV on stable therapy, which might imply some restrictions.

What data supports the idea that Favezelimab + Pembrolizumab for Endometrial Cancer is an effective treatment?

The available research shows that Pembrolizumab, a part of the Favezelimab + Pembrolizumab combination, is effective for treating advanced endometrial cancer, especially in cases with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). Studies like the KEYNOTE-158 trial have shown that Pembrolizumab alone can lead to meaningful responses in these patients. However, there is no specific data provided on the combination of Favezelimab and Pembrolizumab for endometrial cancer in the information available. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Favezelimab + Pembrolizumab for Endometrial Cancer?

Pembrolizumab, one of the drugs in the treatment, has been shown to be effective for advanced endometrial cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), as it helps the immune system attack cancer cells. This effectiveness was demonstrated in the KEYNOTE-158 study, which led to its approval for this type of cancer. ^{1 2 3 4 5}

What safety data exists for Favezelimab + Pembrolizumab in endometrial cancer treatment?

The safety data for pembrolizumab (Keytruda) in combination with lenvatinib for endometrial cancer has been evaluated in several studies. These studies indicate that the combination treatment has a safety profile consistent with each drug as a monotherapy and with the combination in other solid tumors. Adverse events have been characterized, and management strategies have been reviewed to maximize benefits and minimize treatment discontinuation. However, specific safety data for Favezelimab combined with Pembrolizumab in endometrial cancer is not directly addressed in the provided research. ^{2 4 6 7 8}

Is the combination of Favezelimab and Pembrolizumab safe for humans?

Pembrolizumab (also known as Keytruda) has been studied in combination with another drug, lenvatinib, for treating endometrial cancer. Some studies have looked at the safety of this combination, noting that there can be adverse events (unwanted side effects), but these studies focus on pembrolizumab with lenvatinib, not Favezelimab. More specific safety data for Favezelimab combined with Pembrolizumab is not provided in the available research. ^{2 4 6 7 9}

Is the drug Favezelimab and Pembrolizumab a promising treatment for endometrial cancer?

Yes, Pembrolizumab, part of the treatment, is promising for endometrial cancer. It is approved for advanced cases and shows good results when combined with other drugs, improving survival and response rates. ^{2 4 5 10 11}

How is the drug combination of Favezelimab and Pembrolizumab unique for treating endometrial cancer?

The combination of Favezelimab and Pembrolizumab is unique because it involves two immunotherapy drugs that work together to enhance the body's immune response against cancer cells, offering a novel approach compared to traditional chemotherapy or single-agent treatments. ^{2 4 5 10 11}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with certain solid tumors: cutaneous squamous cell carcinoma without distant metastasis, or endometrial cancer that's either stage IVB, recurrent, or metastatic and not suitable for curative surgery. Participants must have progressed after platinum-based chemotherapy and be systemic treatment naïve. They cannot join if they have mismatch repair-deficient tumors.

Inclusion Criteria

My skin cancer is confirmed to be squamous cell carcinoma and can be surgically removed.

My cancer is between Stage II and IV and has not spread far.

My endometrial cancer is at an advanced stage and cannot be treated with surgery or radiation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive coformulated favezelimab/pembrolizumab or pembrolizumab for 3 cycles, each cycle is 21 days

9 weeks

3 visits (in-person)

Adjuvant Treatment

Participants receive additional cycles of treatment to complete a total of 17 cycles

51 weeks

14 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

22 months

Treatment Details

Interventions

• Favezelimab
• Pembrolizumab

Trial Overview The study tests favezelimab coformulated with pembrolizumab (MK-4280A) versus pembrolizumab alone in patients with skin cancer; it also examines lenvatinib plus MK-4280A/pembrolizumab in endometrial cancer patients. The focus is on the complete response rate in skin cancer and objective response rate in endometrial cancer.

Participant Groups

Group I: Pembrolizumab + Lenvatinib (Cohort B) Experimental Treatment 2 Interventions

Participants will receive 200 mg pembrolizumab via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib QD 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.

Group II: Pembrolizumab Experimental Treatment 1 Intervention

Participants will receive 200 mg pembrolizumab via an IV infusion Q3W for 3 cycles in the neoadjuvant period and 14 cycles of adjuvant therapy. Each cycle is 21 days. Participants who do not complete all 3 neoadjuvant cycles should have additional cycles in the adjuvant period so that the total number of study intervention administrations is 17 treatment cycles.

Group III: Favezelimab/Pembrolizumab + Lenvatinib (Cohort B) Experimental Treatment 2 Interventions

Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via IV infusion Q3W for up to 35 cycles (each cycle is 21 days) PLUS lenvatinib every day (QD) 20 mg orally until disease progression, unacceptable toxicity, or discontinuation criteria are met.

Group IV: Favezelimab/Pembrolizumab Experimental Treatment 1 Intervention

Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) via an intravenous (IV) infusion every 3 weeks (Q3W) for 3 cycles in the neoadjuvant period and 14 cycles of adjuvant therapy. Each cycle is 21 days. Participants who do not complete all 3 neoadjuvant cycles should have additional cycles in the adjuvant period so that the total number of study intervention administrations is 17 treatment cycles.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead 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

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.

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]

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]

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]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

In a study of 44 women with advanced or recurrent MMRd/MSI-H endometrial adenocarcinomas treated with pembrolizumab, obesity (BMI≥30) was linked to a higher disease control rate (85.2%) compared to those with a BMI<30 (59.8%).

Patients with obesity also experienced significantly longer progression-free survival (PFS) while overall survival (OS) rates remained similar regardless of BMI, suggesting that body weight may influence treatment outcomes with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. Bernard, L., How, JA., Patel, S., et al.[2023]

In a study of 70 patients with recurrent endometrial cancer, a lower starting dose of lenvatinib (14 mg daily) combined with pembrolizumab was found to be safe and effective, showing similar response rates compared to the recommended dose (20 mg).

Patients with carcinosarcoma histology experienced notable clinical benefits, with a response rate of 25% and a clinical benefit rate of 58.3%, indicating that this treatment combination may be particularly effective for this subtype of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of the combination of pembrolizumab with recommended or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer. How, JA., Patel, S., Fellman, B., et al.[2022]

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]

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]

The FDA granted accelerated approval for the combination of pembrolizumab and lenvatinib to treat advanced endometrial carcinoma in patients who have not responded to prior therapies, based on a trial of 94 patients showing an objective response rate of 38.3%.

This approval was part of Project Orbis, allowing simultaneous review by multiple countries, highlighting the collaborative effort in expediting access to promising cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab plus Lenvatinib for Endometrial Carcinoma, a Collaborative International Review under Project Orbis. Arora, S., Balasubramaniam, S., Zhang, W., et al.[2021]

The combination of pembrolizumab and lenvatinib has shown promising efficacy in treating advanced endometrial cancer, with previous trials indicating improved objective response rates and survival outcomes compared to standard chemotherapy.

This ongoing phase 3 trial aims to determine if pembrolizumab plus lenvatinib is superior to the chemotherapy regimen of paclitaxel plus carboplatin in newly diagnosed patients, with a target enrollment of about 875 participants and results expected in 2022.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. Marth, C., Tarnawski, R., Tyulyandina, A., et al.[2022]

In a study of 108 patients with advanced endometrial carcinoma, the combination of lenvatinib and pembrolizumab resulted in a 38% objective response rate at 24 weeks, with particularly high efficacy (63.6%) in patients with microsatellite instability (MSI)-high tumors.

The treatment demonstrated a median duration of response of 21.2 months and a median overall survival of 16.7 months, while the combination therapy had a manageable safety profile, with 66.9% of patients experiencing grade 3 or 4 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. Makker, V., Taylor, MH., Aghajanian, C., et al.[2021]

References

1. United States 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. [2022]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. [2022]

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

New Approved Use for Keytruda. [2022]

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

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. [2023]

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

Toxicity and efficacy of the combination of pembrolizumab with recommended or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

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

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

FDA Approval Summary: Pembrolizumab plus Lenvatinib for Endometrial Carcinoma, a Collaborative International Review under Project Orbis. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9/LEAP-001. [2022]

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

Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. [2021]