Study of Cemiplimab Combined With Dabrafenib and Trametinib in People With Anaplastic Thyroid Cancer

A Pilot Study of the Addition of Cemiplimab, an Antibody to PD-1, to the Treatment of Subjects With BRAF-Mutant Anaplastic Thyroid Cancer Who Are No Longer Responding to Dabrafenib and Trametinib

This study is being done to see if adding the study drug, cemiplimab, to the standard therapy with dabrafenib and trametinib is an effective treatment against anaplastic thyroid cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Thyroid Cancer; Anaplastic Thyroid Cancer; BRAF Gene Mutation; BRAF Mutation-Related Tumors
• Intervention / Treatment: Drug: Dabrafenib; Drug: Trametinib

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathological (histologically or cytologically) proven diagnosis of BRAF-V600E mutant ATC (a diagnosis that is noted to be consistent with ATC is acceptable)
• Either Metastatic disease or locoregional disease that is considered not resectable for cure
• Ideally a surgeon should determine that the disease is not resectable for cure, but this can also be done by any investigator
• Patients must have measurable disease according to RECIST 1.1 criteria, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as >/= 20 mm with conventional techniques or as >/= 10 mm with spiral CT scan, MRI, or calipers by clinical exam
• Age >/= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status </= (or Karnofsky performance score >/= 60)
• Able to swallow and retain orally administered medication

• Patient must have normal organ and marrow function as defined below:

  • Absolute neutrophil count >/=1.5 x 10^9/L
  • Hemoglobin >/=8 g/dL
  • Platelets >/=100 x 10^9/L
  • Serum bilirubin </=1.5x institutional ULN (unless the patient has GIlbert's Disease, in which case total bilirubin </=3x institutional ULN)
  • AST and ALT </=2.5x institutional ULN (</=5x institutional ULN if there is liver metastasis)
  • Serum creatinine </=1.5mg/dL or calculated creatinined clearance (Cockcroft-Gault formula) >/=50 mL/min or 24-h urine creatinine clearance >/=50 mL/min
  • Left ventricular ejection fraction greater than or equal to instutional lower limit of normal (LLN) by echocardiogram or multigated acquisition (MUGA)
• Negative pregnancy test (serum or urine) within 14 days of registration for women of childbearing potential. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry and for the duration of study participation. Men treated or enrolled on this protocol must also agree to use adequate contraception before the study, for the duration of study participation, and for 4 months after completion of trametinib administration
• Must agree to allow 2-4 separate biopsies of any malignant lesion. For patients whose biopsies (initial) are deemed as unsafe or contraindicated, they will not be eligible.
• Ability to understand and willingness to sign a written informed consent document. Note: Use of Legally Authorized Representative (LAR) is permitted

Exclusion Criteria:

• Previous documentation or current evidence of treatment with dabrafenib and trametinib.

  ° Exception: (1) Patients who started dabrafenib and tranetinib for ATC at an institution outside of MSK are eligible or (2) with the consent of the PI (Sherman). However, this exception is limited to 8 subjects.

• Active brain metastases, unless an exception is granted by the Principal Investigator.
• Current interstitial lung disease or pneumonitis
• Prior history of idelalisib therapy. Exceptions allowed with the consent of the principal investigator (Dr. Sherman)

• History of retinal vein occlusion (RVO) or central serous retinopathy (CSR):

  ° History of RVO or CSR or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension)

• History or current evidence of cardiovascular risk, including any of the following:

  • Left ventricular ejection fraction (LVEF) <LLN
  • A QT interval corrected for heart rate using the Bazett's formula of QTcB>/=480msec
  • Current evidence of clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for >30 days before enrollment are eligible)
  • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months before treatment
• Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection, which will be allowed)

HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with trametinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy

• Uncontrolled intercurrent illness that would limit compliance with study requirement.

• Inability to receive immunotherapy for the following reasons:

  • Any prior grade >/=3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent or any unresolved irAE grade >1
  • Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Exceptions allowed with the consent of the principal investigator (Dr. Sherman)
  • Active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • History of primary immunodeficiency
  • History of allogeneic organ transplant
  • Known history of previous clinical diagnosis of active tuberculosis (this does not include a history of being PPD positive)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BRAF-mutant ATC; Participants will have a diagnosis of BRAF-V600E mutant Anaplastic Thyroid Cancer	Drug: Dabrafenib; Participants will receive dabrafenib 150 mg orally twice a day; Drug: Trametinib; Participants will receive trametinib 2 mg orally once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate per RECIST 1.1 Criteria	Response and progression will be evaluated by using criteria proposed in RECIST 1.1.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Eric Sherman, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Estimated): June 20, 2026
• Study Completion (Estimated): June 20, 2026

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: January 21, 2020
• First Posted (Actual): January 23, 2020

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Memorial Sloan Kettering Cancer Center; Anaplastic Thyroid Cancer; Cemiplimab; Thyroid Cancer; BRAF Gene Mutation; BRAF-Mutant Anaplastic Thyroid Cancer; BRAF Mutation-Related Tumors; 19-464
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Thyroid Diseases; Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Trametinib; Dabrafenib
• Other Study ID Numbers: 19-464

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No