What is the mechanism of action of this treatment?

Pembrolizumab, a PD-1 inhibitor, blocks the PD-1 pathway to help the immune system recognize and attack cancer cells. Lenvatinib, a tyrosine kinase inhibitor, targets receptors involved in tumor growth and angiogenesis, inhibiting cancer cell proliferation and spread. Pelvic External Beam Radiation Therapy causes DNA damage in cancer cells, leading to cell death and preventing further growth. Understanding these mechanisms helps endometrial cancer patients make informed treatment decisions and comprehend how these therapies target their cancer.

What side effects are associated with this type of intervention?

Common treatments for endometrial cancer, such as pembrolizumab, lenvatinib, and pelvic external beam radiation therapy, have distinct side effect profiles. Pembrolizumab, a PD-1 inhibitor, can cause immune-related adverse events including fatigue, rash, and diarrhea, with severe cases leading to pneumonitis or colitis. Lenvatinib, a tyrosine kinase inhibitor, is associated with hypertension, hypothyroidism, diarrhea, and nausea, with a high incidence of grade ≥3 adverse events. Pelvic external beam radiation therapy can lead to long-term urinary and bowel symptoms, including increased frequency, urgency, and diarrhea. These side effects should be carefully considered when choosing a treatment plan.

What prior FDA approvals exist?

The FDA has granted accelerated approval for the combination of pembrolizumab, a PD-1 inhibitor, and lenvatinib, a tyrosine kinase inhibitor, for the treatment of previously treated metastatic endometrial cancer that is not MSI-H/dMMR. This approval was based on a single-arm trial demonstrating an objective response rate of 38.3%. Additionally, pelvic external beam radiation therapy is being studied in combination with these drugs to enhance treatment efficacy by causing DNA damage to cancer cells.

What other types of research exist?

Promising novel alternatives for endometrial cancer treatment in 2024 include: 1) Dostarlimab (PD-1 inhibitor) which has shown efficacy in mismatch repair-deficient (dMMR) endometrial cancer. 2) PARP inhibitors like Niraparib, which target DNA repair mechanisms and have shown promise in various gynecologic cancers. 3) Anti-angiogenesis agents such as Bevacizumab, which inhibit blood vessel formation in tumors. These alternatives offer different mechanisms of action and have shown potential in clinical settings.

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Tyrosine Kinase Inhibitor

Lenvatinib + Pembrolizumab + Radiation for Endometrial Cancer

Phase 1

Recruiting

Led By Matthew Schlumbrecht, MD, MPH

Research Sponsored by Aaron Wolfson

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if combining an immune-boosting drug, a cancer-fighting pill, and shorter radiation treatments can help treat pelvic area cancer by boosting the immune system, stopping cancer growth, and killing cancer cells.

Who is the study for?

This trial is for women aged 18 or older with recurrent or unresectable endometrial carcinoma that's not mismatch repair deficient. They must have a specific performance status, normal organ and marrow function, no recent investigational drug use, and agree to contraception if of childbearing potential. Exclusions include certain prior treatments, uncontrolled conditions like hypertension or infections (HIV/HBV/HCV), active CNS metastases, other progressing cancers, major surgery recovery, and immunosuppressive therapy within 21 days before the study.

What is being tested?

The trial tests combining pembrolizumab (an immune checkpoint inhibitor) with lenvatinib (a targeted therapy) alongside a shortened course of pelvic radiation therapy in patients with endometrial cancer. The goal is to determine if this combination can prevent cancer cells from multiplying and spreading.

What are the potential side effects?

Potential side effects may include high blood pressure due to lenvatinib; fatigue, skin reactions, or autoimmune-like symptoms from pembrolizumab; and typical radiation-associated discomfort such as localized skin irritation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Events of Treatment-Related Toxicity

Recommended Phase 2 Dose (RP2D) of Lenvatinib

Secondary study objectives

Number of Reported Adverse Events

Overall Response Rate (ORR)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Lenvatinib, Pembrolizumab and Hypofractionated (Hypofx) External Beam Radiation Therapy (EBRT) GroupExperimental Treatment3 Interventions

Participants in this group will receive a combination treatment of Lenvatinib, Pembrolizumab, and Hypofx Pelvic EBRT over a period of approximately 10 to 12 weeks. 1. Lenvatinib - administered in a 3 plus 3 escalation/de-escalation design. Participants will receive 1 of 4 of the following dose levels: Dose level 1- 4 mg Dose level 2- 8 mg Dose level 3 (Starting dose) - 12 mg Dose level 4- 16 mg 2. Pembrolizumab- 200 mg IV will be administered on Day 1, 22 and 43 3. HypoFx whole pelvic EBRT begins on Day 22 and continues for a total of 16 fractions of radiation given at a dose of 2.5 Gy per fraction for a total dose of 40.0 Gy delivered to the pelvis. A pelvic boost HypoFx EBRT consisting of 7 fractions of radiation given at a dose of 2.5 Gy per fraction that will be delivered to site(s) of gross disease of at least 1.0 cm in size. An additional boost total dose of 17.5 Gy administered will be administered over a period of 1.5 to 2.0 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lenvatinib

2017

Completed Phase 4

~2070

Pembrolizumab

2017

Completed Phase 3

~3150

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Pembrolizumab, a PD-1 inhibitor, blocks the PD-1 pathway to help the immune system recognize and attack cancer cells. Lenvatinib, a tyrosine kinase inhibitor, targets receptors involved in tumor growth and angiogenesis, inhibiting cancer cell proliferation and spread. Pelvic External Beam Radiation Therapy causes DNA damage in cancer cells, leading to cell death and preventing further growth. Understanding these mechanisms helps endometrial cancer patients make informed treatment decisions and comprehend how these therapies target their cancer.

Lenvatinib in Management of Solid Tumors.Second-line lenvatinib in patients with recurrent endometrial cancer.