Lenvatinib and Pembrolizumab in Differentiated Thyroid Cancers (DTC)
Combination Targeted Therapy With Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers: A Phase II Study
3 other identifiers
interventional
57
1 country
7
Brief Summary
This phase II trial studies how well pembrolizumab and lenvatinib work in treating patients with differentiated thyroid cancer that has spread to other places in the body or has come back and cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2018
Longer than P75 for phase_2
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 23, 2016
CompletedFirst Posted
Study publicly available on registry
November 28, 2016
CompletedStudy Start
First participant enrolled
February 7, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 15, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
October 8, 2023
CompletedResults Posted
Study results publicly available
October 24, 2023
CompletedAugust 29, 2025
August 1, 2025
4.5 years
November 23, 2016
July 5, 2023
August 27, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Complete Response Rate (Cohort 1)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will use a one-stage binomial design.
26 months
Confirmed Response Rate (Cohort 2)
Assessed by RECIST 1.1. Will use a 2-stage Simon Optimal MinMax design.
27 months
Secondary Outcomes (3)
Number of Patients Experiencing Grade 3+ Adverse Events
27 months
Progression Free Survival (PFS)
12 months
Overall Survival (OS)
12 months
Other Outcomes (1)
Biomarker Levels Analysis Following Pembrolizumab and Lenvatinib Combination Therapy
Up to 3 years
Study Arms (1)
Treatment (lenvatinib, pembrolizumab)
EXPERIMENTALPatients receive lenvatinib PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles.
Interventions
Given PO
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- Locally recurrent and unresectable and/or distant metastatic differentiated thyroid cancer (DTC), histologically or cytologically confirmed; the diagnosis of DTC includes the following subtypes: papillary thyroid cancer (PTC) (including but not limited to variants such as follicular variant, tall cell, columnar cell, Hurthle cell variant of papillary carcinoma, and poorly differentiated), follicular thyroid cancer (FTC), including insular variant, Hurthle cell carcinoma and poorly differentiated thyroid cancer
- Measurable disease meeting the following criteria:
- At least 1 lesion of \>= 1.0 cm in the longest diameter for a non-lymph node or \>= 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI); if there is only one target lesion and it is a non-lymph node, it should have a longest diameter of \>= 1.5 cm
- Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
- For cohort 1 only: evidence of disease progression =\< 14 months prior to registration according to RECIST 1.1, as confirmed by the site study principal investigator (PI)
- For cohort 2 only: progressive disease (PD) on lenvatinib per RECIST 1.1 =\< 60 days prior to registration, as confirmed by the site study PI; patients need to have documented imaging and measurement of RECIST target lesions within 30 days of starting pembrolizumab
- Radioiodine (RAI)-resistant disease as defined by one or more of the following criteria:
- One or more measurable lesions that do not demonstrate RAI uptake
- One or more measurable lesions progressive by RECIST 1.1 =\< 14 months of prior RAI therapy
- One or more measurable lesions present after cumulative RAI dose of \>= 600 mCi
- One or more measurable lesions that are fludeoxyglucose F-18 (FDG)-avid (\> 5 standardized uptake value \[SUV\]), if positron emission tomography (PET)/CT scan performed; these lesions may also be RAI-avid
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Absolute neutrophil count (ANC) \>= 1,500 /mcL (obtained =\< 30 days prior to registration)
- Platelets \>= 100,000 / mcL (obtained =\< 30 days prior to registration)
- Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin dependency (=\< 7 days prior to registration) (obtained =\< 30 days prior to registration)
- +13 more criteria
You may not qualify if:
- Cohort 1 only: prior treatment with previous VEGFR active multikinase inhibitor
- Cohort 2 only: discontinued lenvatinib due to toxicity
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Female subjects of childbearing potential: unwilling or unable to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; NOTE: subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year
- Male subjects: unwilling or unable to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive (HIV 1/2 antibodies) and currently receiving antiretroviral therapy
- Currently participating and receiving study therapy (except lenvatinib for patients in cohort 2) or has participated in a study of an investigational agent and received study therapy within 4 weeks prior to registration
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy =\< 7 days prior to the first dose of trial treatment
- Known history of active TB (Bacillus tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients
- Prior anti-cancer monoclonal antibody (mAb) =\< 4 weeks prior to registration or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered \>= 4 weeks prior to registration
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 (except lenvatinib for patients in cohort 2) or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
- NOTE:
- Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502, United States
University of Colorado Hospital
Aurora, Colorado, 80045, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Baste N, Mora M, Grau JJ. Emerging systemic antitarget treatment for differentiated thyroid carcinoma. Curr Opin Oncol. 2021 May 1;33(3):184-195. doi: 10.1097/CCO.0000000000000727.
PMID: 33720068DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bryan Haugen, M.D.
- Organization
- University of Colorado, School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Bryan R Haugen
Academic and Community Cancer Research United
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 23, 2016
First Posted
November 28, 2016
Study Start
February 7, 2018
Primary Completion
August 15, 2022
Study Completion
October 8, 2023
Last Updated
August 29, 2025
Results First Posted
October 24, 2023
Record last verified: 2025-08