Pembrolizumab and Lenvatinib in Patients With High Risk Locally Advanced Cervix Cancer

NCT07368985 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2023-506982-73-00
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if the combination of Pembrolizumab and Lenvatinib works to treat locally advanced cervical cancer in adults that will undergo primary chemoradiation and brachytherapy. It will also learn about the safety of the combination of Pembrolizumab and Lenvatinib. The main questions it aims to answer are:

• Does the combination of Pembrolizumab and Lenvatinib improve progression free survival at two years after treatment?
• What side effects do participants have when taking the combination of Pembrolizumab and Lenvatinib? Researchers will compare the combination of Pembrolizumab and Lenvatinib to existing results with primary chemoradiatoin and brachytherapy to see if the combination of Pembrolizumab and Lenvatinib works to treat locally advanced cervical cancer. Participants will:
• Visit the clinic to receive Pembrolizumab intra venously once every 3 weeks for 5 cycles and then once very 6 weeks for a maximum of 2-years
• Take Lenvatinib orally every day starting at the earliest 8 weeks after the last brachytherapy to a maximum of 1 year
• Visit the clinic for checkups and tests during scheduled visits

Conditions

Cervical Cancer by FIGO Stage 2018; Squamous Cell Carcinoma FIGO 2018 Stage IIIA, IIIB, IIIC1-IIIC2; Adenocarcinoma or Adeno-squamous Carcinoma Stage IB3-IIIC2

Keywords

cervical cancer; locally advanced cervical cancer; Pembrolizumab; Lenvatinib; radiotherapy; brachytherapy; high risk locally advanced cervical cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Actuarial Progression free survival (PFS) rate at 24 months, with a PFS event defined by either progression, using investigator assessed RECIST 1.1, or by death from any cause.

  From date of enrollment to 24 months

Secondary Outcomes (6)

• Overall Survival

  From date of enrollment to 24 and to 36 months

• Progression Free Survival

  From date of enrollment to 36 months

• Local Control

  From date of enrollment to 24 and to 36 months.

• Regional Nodal Control

  From date of enrollment to 24 and to 36 months.

• Adverse Events

  From date of enrollment to 24 and 36 months.

Study Arms (1)

Single arm: Pembrolizumab and Lenvatinib

EXPERIMENTAL

Single arm open label study of Pembrolizumab and Lenvatinib in patients with high risk locally advanced cervix cancer that will undergo chemoradiation and brachytherapy

Drug: pembrolizumab and lenvatinib

Interventions

pembrolizumab and lenvatinib DRUG

Patients will undergo standard of care chemoradiation (CRT: combined external beam radiotherapy with weekly cisplatin) followed by MRI guided brachytherapy, this will be combined with the following study drugs: Pembrolizumab: 5 intravenous administrations of Pembrolizumab (200 mg) every 3 weeks with the first administration at the start of chemoradiotherapy, followed by subsequent doses of 400 mg IV Pembrolizumab at 6 weeks intervals, starting week 16 up to week 102 with a maximum of 15 cycles. Lenvatinib: the combination with Lenvatinib will start after recovery, along with the 6 weekly cycles of Pembrolizumab, e.g. around 8-9 weeks after brachytherapy (week 16), at a dose of 20 mg daily oral and will continue up to week 48.

Single arm: Pembrolizumab and Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• High risk defined by either of the criteria:
• Squamous cell carcinoma FIGO 2018 stage IIIA, IIIB, IIIC1-IIIC2 OR
• Adenocarcinoma or adeno-squamous carcinoma Stage IB3-IIIC2.
• Have adequate haematological parameters and organ function as defined in the protocol Table 3.
• Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg.
• Have measurable disease based on RECIST 1.1 on imaging at diagnosis.
• The participant provides written informed consent for the trial.
• Patients should have been planned for radical chemoradiation and MR guided adaptive brachytherapy with intended treatment completion within 50 days.
• Patients should be deemed suitable for start of Pembrolizumab during chemoradiation and brachytherapy, and for start of Lenvatinib/Pembrolizumab 8 weeks after last brachytherapy as per local investigators assessment.
• Criteria for known Hepatitis B and C positive subjects:
• Hepatitis B and C screening tests are not required unless:
• Known history of HBV or HCV infection
• As mandated by local health authority

You may not qualify if:

• Patients with locally advanced cervical cancer and signs of organ wall involvement on MRI or non-gastrointestinal fistula.
• Major surgery within 3 weeks prior to first dose of study interventions. Brachytherapy is not considered a major surgery.
• Urine protein ≥1 g/24 hours. Note: Participants with proteinuria ≥2+ (≥100 mg/dL) on urine dipstick testing (or urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
• If a MUGA or cardiac ultrasound was performed (on clinical indication): having a LVEF below the institutional (or local laboratory) normal range.
• Radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation NOTE: the degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following Lenvatinib therapy.
• Prolongation of QTcF interval to \>480 ms. NOTE: If the QTcF is prolonged to \>480 ms in the presence of a pacemaker, contact the Sponsor to determine eligibility.
• Clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
• Note: Medically controlled arrhythmia would be permitted.
• Gastrointestinal malabsorption or any other condition that might affect the absorption of Lenvatinib.
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• WOCBP who has a positive urine pregnancy test within 72 hours prior to adjuvant phase. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note eligible patients for this trial are not WOCBP due to treatment with CRT.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• Severe hypersensitivity (≥Grade 3) to Pembrolizumab or Lenvatinib and/or any of its excipients.

Sponsors & Collaborators

• Prof. Dr. Remi A. Nout: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

Location

MeSH Terms

Conditions

Adenocarcinoma; Uterine Cervical Neoplasms

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

Remi A Nout, MD PhD

CONTACT

+31 107041366; r.nout@erasmusmc.nl

Ingrid Boere, MD

CONTACT

+31 107034897; i.boere@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 22, 2026
• First Posted: January 27, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: January 27, 2026

Record last verified: 2026-01

Locations

NL (1)