A Phase II single arm open label study of Pembrolizumab and Lenvatinib in patients with high risk locally advanced cervix cancer: an EMBRACE high risk study initiative

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-11-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate progression free survival (PFS) at 24 months (by investigator assessed RECIST 1.1) in women with high-risk locally advanced cervical cancer treated with chemoradiotherapy and Pembrolizumab followed by Pembrolizumab and Lenvatinib

Secondary objectives 7

1. To evaluate adverse event profile and compliance of the concurrent and adjuvant combination regimen.
2. To evaluate 2-year and 3-year local and regional (pelvic and para-aortic) control.
3. To report 3-year PFS and 2- and 3-year overall survival (OS).
4. To evaluate biomarkers for response and overall outcomes on blood and tissue samples collected for translational research.
5. To evaluate impact of irradiated volumes on immune mediated systemic response.
6. To evaluate impact of systemic therapy on patient reported outcomes using EORTC QLQC30 and Cx-24. In addition, cumulative symptom burden will be investigated.
7. To exploratory test the feasibility of correlating outcomes with multiparametric MRI including dynamic contrast enhanced imaging (if available in participating centres)

Conditions and MedDRA coding

high risk or poor response after chemoradiation and brachytherapy for locally advanced cervix cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. age >18 years
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. High risk defined by either of the criteria: a. Squamous cell carcinoma FIGO 2018 stage IIIA, IIIB, IIIC1-IIIC2 OR b. Adenocarcinoma or adeno-squamous carcinoma Stage IB3-IIIC2.
4. Have adequate haematological parameters and organ function
5. Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg.
6. Have measurable disease based on RECIST 1.1 on imaging at diagnosis.
7. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
8. Patients should have been planned for radical chemoradiation and MR guided adaptive brachytherapy with intended treatment completion within 50 days.
9. 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.
10. 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 Hepatitis B positive subjects: • Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to inclusion. • Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.

Exclusion criteria 21

1. Patients with locally advanced cervical cancer and signs of organ wall involvement on MRI or non-gastrointestinal fistula.
2. Major surgery within 3 weeks prior to first dose of study interventions. Brachytherapy is not considered a major surgery.
3. 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.
4. If a MUGA or cardiac ultrasound was performed (on clinical indication): having a LVEF below the institutional (or local laboratory) normal range.
5. Radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
6. Prolongation of QTcF interval to >480 ms.
7. 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.
8. Gastrointestinal malabsorption or any other condition that might affect the absorption of Lenvatinib.
9. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
10. 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.
11. 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.
12. 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.
13. Severe hypersensitivity (≥Grade 3) to Pembrolizumab or Lenvatinib and/or any of its excipients.
14. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
15. History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
16. Active infection requiring systemic therapy.
17. Known history of Human Immunodeficiency Virus (HIV) infection.
18. Known concurrent active Hepatitis B (defined as HBsAg positive and detectable HBV DNA) and/or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA [qualitative]) infection.
19. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
20. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
21. Has had an allogenic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Actuarial Progression free survival (PFS) rate at 24 months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Prof. dr. R.A. Nout

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Prof. dr. R.A. Nout

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications