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Thyroid CancerPhase 2NCT04544111

PDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer

A Phase 2 study testing Trametinib, Dabrafenib and PDR001 in people with Thyroid Cancer and Thyroid Cancer, Follicular, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to find out whether a drug called PDR001, combined with either trametinib or dabrafenib, is a safe and effective treatment for thyroid cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Trametinib, Dabrafenib and PDR001
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
7 sitesUnited States
Study dates
2 Sep 2020to 2 Sep 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cohort A Only: Confirmation in a CLIA certified laboratory that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastases) does not possess a BRAFV600- mutation (non-V600- BRAF mutations, including BRAF translocations, may be included in this cohort).
  • Cohort A Only: Evidence of progressive disease (e.g. presence of new or growing lesion(s) on radiologic imaging and/or new or worsening tumor-related symptoms) within 14 months of study enrollment
  • Cohort B Only: Confirmation in a CLIA certified laboratory that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastases) possesses a BRAFV600- mutation (e.g. V600E, V600K, V600D).
  • Cohort B Only: Patients must have documented progression (evidence of tumor growth or appearance of new tumor) on prior BRAF directed therapy (e.g. (but not limited to) vemurafenib, dabrafenib) and must have tolerated this therapy without > Grade 3 toxicity on their most recent evaluation (excluding Grade 4 asymptomatic laboratory abnormalities).
  • Patients must have pathologically or cytologically confirmed differentiated thyroid cancer of follicular origin (including papillary thyroid carcinoma, follicular thyroid carcinoma, hurthle cell carcinomas, poorly differentiated thyroid carcinoma and their respective variants).
  • Patients must have RECIST v1.1 measurable disease.
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  • Patients must have recurrent or metastatic disease not amenable to curative surgery or radiation.
  • Age > 18 years.
  • ECOG performance status of 0 or 1.
  • Patients must have no recent treatment for thyroid cancer as defined as:
  • No prior RAI therapy is allowed <6 months prior to initiation of therapy on this protocol. A diagnostic study using <10 mCi of RAI is not considered RAI therapy
  • No external beam radiation therapy <4weeks prior to initiation of therapy on this protocol.
  • No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed <4 weeks prior to the initiation of therapy on this protocol (an exception to this are patients on dabrafenib who will be enrolling into Cohort B). Dabrafenib may be continued prior to and through trial enrollment into the start of the study therapy when PDR001 will be added to dabrafenib
  • RAI-refractory disease on structural imaging, defined as one of the following:
  • Total lifetime dose of radioiodine > 600 mCi
  • A tumor that is not radioiodine-avid on a diagnostic radioiodine scan performed prior to enrollment in the current study.
  • A radioiodine-avid metastatic lesion which remained stable in size or progressed despite radioiodine treatment 6 months or more prior to study entry in the study. There are no size limitations for the index lesions used to satisfy this entry criterion
  • The presence of at least one fluorodeoxyglucose (FDG) avid lesion.
  • Patients must be able to swallow and retain orally-administered pills without any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or bowels.
  • Patients must have tissue from the primary tumor or metastases available for correlative studies. Either a paraffin block or at least 20 unstained slides are acceptable (30 unstained slides would be ideal). (If less than twenty unstained slides are available and a paraffin bloc is not available, the patient may be able to participate at the discretion of the investigator).
  • Patients must agree to undergo two research biopsies of (a) malignant lesion(s). Tumor tissue obtained prior to study consent or treatment as part of standard of care can also be submitted in lieu of performance of the first pre-treatment biopsy if the Principal Investigator deems it to be of sufficient quantity/quality/timeliness. Patients may be exempt from biopsy if 1) the investigator or person performing the biopsy judges that no tumor is accessible for biopsy, 2) the investigator or person performing the biopsy feels that the biopsy poses too great of a risk to the patient, or 3) the patient cannot be safely removed from anti-coagulation therapy (if the anti-coagulation therapy needs to be temporarily held for the biopsy procedure). If the only tumor accessible for biopsy is also the only lesion that can be used for RECIST v1.1 response evaluation, then the patient may be exempt from biopsy. If the investigator deems a second research biopsy to be high risk after a patient has completed the first research biopsy, the patient may be exempt from the second biopsy.
  • Screening laboratory values must meet the following criteria:
  • WBC ≥ 2000/µl
  • Neutrophils ≥ 1500/µl
  • Platelets ≥ 100 x 10^3/µl
  • Hemoglobin > 9.0 g/dL
  • AST/ALT ≤ 3 x ULN
  • Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
  • Female CrCl = (140 - age in years) x weight in kg x 0.85/72 x serum creatinine in mg/dL
  • Male CrCl = (140 - age in years) x weight in kg x 1.00/72 x serum creatinine in mg/dL
  • Left ventricular ejection fraction ≥ institutional lower limit of normal by transthoracic echocardiogram (ECHO) performed within 1 month of study drug initiation.

Who cannot join

  • Cohort A Only:
  • Patients with the following ophthalmological finding/conditions:
  • Intraocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intraocular pressure).
  • Current or past history of central serous retinopathy or retinal vein occlusion.
  • Cohort A Only: Prior therapy with a MEK 1/2 targeted drug (with the exception of patients who received this therapy for a defined period of time to enhance radioiodine activity).
  • Symptomatic metastatic brain or leptomeningeal tumors (asymptomatic or treated metastatic brain or leptomeningeal tumors are allowed).
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  • Prior therapy directed at the PD1/PD-L1 axis.
  • Any of the following cardiovascular risks:
  • A QT interval corrected for heart rate using the Bazett's formula QTcB ≥ 480 msec.
  • Clinically significant uncontrolled arrhythmias (Exception: patients with controlled atrial fibrillation for >30 days prior to enrollment are eligible).
  • Acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months of enrollment.
  • ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  • Treatment-refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic >90 mmHg which cannot be controlled by anti-hypertensive therapy.
  • Prior malignancy if treated within 2 years of trial drug initiation (with the exception of non-melanoma skin cancers). Patients may be included if they have completed therapy for a prior malignancy >2 years prior to drug initiation and are currently NED.
  • Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
  • Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy (including but not limited to methotrexate, azathioprine, and TNF-alpha blockers) 7 days prior to planned first date of study treatment (note: topical, inhaled, nasal, intra-articular and ophthalmic steroids are allowed).
  • Active, known or suspected autoimmune disease or documented history of autoimmune disease with the exception of vitiligo, controlled type I diabetes mellitus on stable insulin, autoimmune thyroid disease or psoriasis not requiring systemic treatment.
  • Allogenic bone marrow or solid organ transplant.
  • History of severe hypersensitivity reactions to monoclonal antibodies or any other study drug components which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
  • Known history of current interstitial lung disease or non-infectious pneumonitis.
  • Patients with active hepatitis B infection (HBV surface antigen positive).
  • Subject is known to be positive for Human Immunodeficiency Virus (HIV) or active Hepatitis C Virus (HCV). Testing for HIV or Hepatitis C prior to initiation of the study drug is not required. If a patient has a known history of treated HCV, then a viral load is required to confirm clearance of infection.
  • Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test within 72 hours prior to initiating study treatment.
  • Women of child-bearing potential (as defined in Appendix 18.3), unless they are using highly effective methods of contraception during dosing and for 150-days after stopping treatment with PDR001. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient
  • Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. NOTE: In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
  • Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
  • Sexually active males unless they use a condom during intercourse while on treatment and for 150 days after stopping treatment with PDR001 and should not father a child in this period. A condom is required to be used by vasectomized men as well during intercourse to prevent delivery of the drug via semen.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (Limited protocol activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Limited protocol activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (Limited protocol activities)

    Rockville Centre, New York, 11553

Other trials in United States

About this study

Official title: Phase II Study of PDR001 in Combination With MAPK Pathway Inhibitors in Patients With Radioiodine-Refractory Thyroid Cancer

The purpose of this study is to find out whether a drug called PDR001, combined with either trametinib or dabrafenib, is a safe and effective treatment for thyroid cancer.

Being tested
Trametinib, Dabrafenib, PDR001
Keywords
Thyroid Cancer, PDR001, Radioiodine-Refractory Thyroid Cancer, Memorial Sloan Kettering Cancer Center, 20-258
Medical subject headings
Thyroid Neoplasms, Thyroid cancer, follicular, Thyroid Cancer, Papillary, Adenocarcinoma, Follicular, Adenoma, Oxyphilic, Thyroid cancer, Hurthle cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrametinibDrug

    2mg by mouth daily

    *If patient loses the ability to swallow while on study, trametinib may be provided as a powder in bottle for reconsititution. Trametinib, as a powder in bottle, will be mixed with sterile/purified water into an oral solution and administered PO or through enteral feeding tube

  • DabrafenibDrug

    150 mg twice daily (OR at dose the patient previously tolerated)

  • PDR001Drug

    400mg IV every 4 weeks

Study groups in NCT04544111
Study groupRoleWhat they receive
Cohort A-BRAF WT tumorsExperimentalCohort A (BRAF WT tumors): trametinib (T) 2mg by mouth daily plus PDR001 400mg IV every 4 weeks
Receives: Drug: Trametinib; Drug: PDR001
Cohort B-BRAF MutantExperimentalCohort B (BRAF Mutant, resistant to previous BRAF inhibitors): dabrafenib (D) 150 mg twice daily (OR at dose the patient previously tolerated) plus PDR001 400mg IV every 4 weeks.
Receives: Drug: Dabrafenib; Drug: PDR001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate

    The primary endpoint is to determine the overall response rate (ORR=CR+PR) as documented by RECIST v1.1 criteria within each cohort.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2020
  2. Study start2 Sep 2020
  3. Primary completion2 Sep 2027 (estimated)
  4. Study completion2 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04544111
Sponsor's protocol ID
20-258
Status last verified
Sep 2026
First submitted
3 Sep 2020
Last updated
17 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trametinib, Dabrafenib and PDR001 in people with Thyroid Cancer and Thyroid Cancer, Follicular, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04544111.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.

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