Efficacy of Pembrolizumab and Lenvatinib in Patients With Anaplastic Thyroid Cancer

August 29, 2025 updated by: Ernest Dzhelialov, Saint Petersburg State University, Russia
This pilot phase 2 study evaluate the effectiveness and safety of pembrolizumab and lenvatinib in patients with anaplastic thyroid cancer. Patients with anaplastic thyroid cancer who are treatment-naive (BRAF-negative) and who were previously treated with chemptherapy or targeted therapy are scheduled to undergo pembrolizumab and lenvatinib and evaluate the outcomes according to the primary and secondary endpoints.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The aim of the study was to demonstrate the efficacy and safety of pembrolizumab and lenvatinib in patients with anaplastic thyroid cancer.

Scientific hypothesis: the combination of pembrolizumab and lenvatinib is effective and safe in patients with anaplastic thyroid cancer.

Trial design, materials and methods: this study is a pilot Phase 2 study. This study is prospective and open-label. Patients who meet the criteria will be treated with a combination of pembrolizumab and lenvatinib and outcomes will be assessed according to primary and secondary endpoints.

All patients will receive one regimen of antitumor treatment (exploratory therapy). The control will be carried out by monitoring the initial state in dynamics.

Before starting research therapy, data will be recorded for each patient in an individual registration card.

Before starting research therapy, clinical and laboratory parameters will be evaluated and computed tomography of the brain, neck, thoracic and abdominal cavities with intravenous contrast will be performed (initial assessment of the prevalence of the tumor process).

Mutations in the BRAF V600 gene, microsatellite instability (MSI) and PD-L1 expression will be determined in the tumor material (first of all), and the following molecular genetic variants will be determined in the second place (planned): RET, NTRK, ALK, ROS1.

Research therapy includes pembrolizumab 200 mg intravenously for 30 minutes (cycle 21 days) in combination with targeted therapy with lenvatinib 20 mg (2 capsules of 10 mg 1 time per day daily). Dose modification in case of toxicity for pembrolizumab is not provided. For lenvatinib, a sequential dose reduction is provided depending on the previous level (14 mg, 10 mg, 8 mg). When the dose is reduced, a return to the previous level is not carried out.

Duration of treatment: pembrolizumab - up to 35 cycles, until progression or intolerable toxicity, depending on what comes first. Lenvatinib - before progression or intolerable toxicity.

Follow-up period of patients:

follow-up during active treatment within the framework of the study - before progression or intolerable toxicity; patient survival monitoring - documenting subsequent lines of antitumor treatment before the patient's death or loss of contact with him; patient safety monitoring - 30 and 90 days from the date of the final dose.

Assessment of the response to treatment (assessment of clinical and laboratory parameters, computed tomography of the brain, neck, thoracic and abdominal cavities with intravenous contrast) will be carried out monthly or according to clinical indications in the first 6 months, then - according to the decision of the research team. Based on the results of the control study, the response to treatment will be evaluated according to the iRECIST criteria. Patients who meet the criteria for progression will be excluded from the study.

When converting a tumor to resectability and planning surgical treatment, it is recommended to suspend taking lenvatinib at least a week before surgery and resume taking it at least 2 weeks after. There is no relationship between pembrolizumab and complications associated with surgical treatment, and no interruptions in treatment are required.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Russia
      • Saint Petersburg, Russia, 190020
        • Recruiting
        • Saint Petersburg State University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • immunohistochemically verified anaplastic thyroid cancer that is not eligible to R0-R1 surgery;
  • age ≥ 18 years;
  • functional status of ECOG 0-2;
  • adequate function of internal organs and bone marrow;
  • the ability to give written informed consent.

Exclusion Criteria:

  • patients with a mutation in the BRAF V600 gene without previous targeted therapy with BRAF/MEK inhibitors;
  • patients with clinically significant hemoptysis and bleeding (for example, from the gastrointestinal tract or tumor-associated bleeding);
  • tumor invasion into large vessels;
  • patients with open wounds and fistulas;
  • contraindications to taking any of the studied drugs;
  • patients with poor functional status (ECOG 3-4);
  • continuous use of immunosuppressive therapy;
  • prior therapy with investigational drugs;
  • pregnancy, breast-feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention group
Treatment-naive patients with BRAF-negative anaplastic thyroid cancer and previously treated patients, including patients with BRAF-positive anaplastic thyroid cancer (resistant to anti-BRAF therapy).
Drug: Pembrolizumab + Lenvatinib
Pembrolizumab is a programmed death receptor-1 (PD-1)-blocking antibody. Lenvatinib is Lenvatinib is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability assessment (Incidence of Treatment-Emergent Adverse Events)
Time Frame: Each visit (every 21 days) assessed up to 48 months
Safety assessment will be assessed on the basis of adverse events (according to CTCAE 5.0)
Each visit (every 21 days) assessed up to 48 months
Objective response rate
Time Frame: Each month from date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
The proportion of participants with a partial or complete response to the therapy. It is determined according to the iRECIST criteria.
Each month from date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Progression-Free Survival
Time Frame: 6-month, 1-year, 2-year
The time from the date of treatment initiation to the radiological progression or death of the patient for any reason.
6-month, 1-year, 2-year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 6-month, 1-year, 2-year
The time from the start date of treatment to the death of the patient for any reason.
6-month, 1-year, 2-year
The assessment of conversion to resectability
Time Frame: Each month from date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
The proportion of participants with an initially unresectable or potentially resectable tumor who have moved to a resectable during treatment.
Each month from date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Saint Petersburg State University, Russia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 25, 2024

Primary Completion (Estimated)

March 25, 2026

Study Completion (Estimated)

June 25, 2026

Study Registration Dates

First Submitted

March 27, 2024

First Submitted That Met QC Criteria

April 16, 2024

First Posted (Actual)

April 18, 2024

Study Record Updates

Last Update Posted (Estimated)

September 5, 2025

Last Update Submitted That Met QC Criteria

August 29, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 33

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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