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NCT03753919: DUTHY

Durvalumab Plus Tremelimumab for the Treatment of Patients With Progressive, Refractory Advanced Thyroid Carcinoma -The DUTHY Trial

Terminated Phase 2 Results posted Last updated 11 March 2026
What this trial tests

Phase 2 trial testing Durvalumab in Metastatic Thyroid Papillary Carcinoma in 79 participants. Terminated before completion.

Timeline
2 April 2019
Primary endpoint
8 November 2024
8 November 2024

Quick facts

Lead sponsorGrupo Espanol de Tumores Neuroendocrinos
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment79
Start date2 April 2019
Primary completion8 November 2024
Estimated completion8 November 2024
Sites15 locations across Spain

Drugs / interventions tested

Conditions studied

Sponsor

Grupo Espanol de Tumores Neuroendocrinos — full company profile →

Who can join

18 and older, any sex, with Metastatic Thyroid Papillary Carcinoma or Metastatic Thyroid Follicular Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival Rate at 6 Months Primary · Throughout the study period, up to 6 months from start of treatment

6-months progression-free survival by Response Evaluation Criteria in Solid Tumors (RECIST v1.1), which is defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) at 24 weeks after durvalumab plus tremelimumab was started without observing disease progression or death at this time point. Per RECIST for target lesions, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor su

GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)32.420.4 – 51.6
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)40.926.3 – 63.6
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)33.315.0 – 74.2
Overall Survival Rate at 6 Months Primary · Throughout the trial period, up to 6 months from first dose of treatment.

Defined as percentage of patients alive at month 6 from first dose of treatment.

GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)70.356.7 – 86.7
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)96.690.1 – 100
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)65.643.2 – 99.8
Overall Survival, Median Secondary · Throughout the trial period, with a following up to 4 years from the start of treatment

Median OS, defined as the time from the start of treatment until death (patients without events were censored at the last follow-up). Estimated by Kaplan-Meier

GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)13.89.4 – 32.8
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)35.530.1 – NA
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)13.85.7 – NA
Overall Survival Rate at 18 Months Secondary · Throughout the trial period, up to 18 months from first dose of treatment.

Percentage of patients alive at month 18 from first dose of treatment.

GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)41.528.0 – 61.4
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)78.865.3 – 97.5
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)46.925.0 – 87.9
Progression-free Survival (PFS), Median Secondary · Throughout the trial period, a median follow-up period 14 months from the start of treatment

median PFS, defined as the time from the start of treatment until disease progression (PD) according to RECIST v1.1 or death (patients without events were censored at the last tumor assessment). Estimated by Kaplan-Meier. Per RECIST v1.1, PD: for target lesions, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. For non-target lesions: unequivocal progression of existing non-target lesions or appearance of new lesions.

GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)3.72.7 – 6.5
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)5.32.8 – 23.2
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)3.62.2 – NA
Progression-free Survival Rate at 18 Months Secondary · Throughout the study period, up to 18 months from start of treatment

18-months progression-free survival by Response Evaluation Criteria in Solid Tumors (RECIST v1.1), which is defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) at 18 months after durvalumab plus tremelimumab was started without observing disease progression or death at this time point. Per RECIST for target lesions, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor

GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)6.01.6 – 22.6
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)26.513.6 – 51.6
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)8.31.3 – 54.4
Overall Response Rate (ORR) Secondary · Through study completion, average 1 year

Defined as patients who achieved partial response (PR) or complete response (CR) as best response according to RECIST 1.1 criteria or iRECIST 1.1 criteria

GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)8
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)10
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)33
Overall Response (OR) Best Response According to RECIST 1.1 Secondary · Throughout the trial period, with a following up to 4 years from the start of treatment

Defined as patients who achieved partial response (PR) or complete response (CR) as best response according to RECIST 1.1 criteria Per RECIST for target lesions, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For non-target lesions, CR: Disappearance of all non-target lesions.

SD
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)48.6
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)50.0
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)25.0
PD
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)29.7
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)36.7
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)41.7
PR
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)8.1
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)10.0
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)33.3
CR
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)0.0
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)0.0
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)0.0
Unknown
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)13.5
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)3.3
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)0
Overall Response (OR) Best Response According irRecist Criteria Secondary · Throughout the trial period, with a following up to 4 years from the start of treatment

Defined as patients who achieved partial response (PR) or complete response (CR) as best response according to irRecist criteria.

SD
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)48.6
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)53.3
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)25.0
PD
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)27.0
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)33.3
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)33.3
PR
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)8.1
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)10.0
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)25.0
CR
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)0.0
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)0.0
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)8.3
Not evaluable
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)2.7
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)0
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)8.3
Unknown
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)13.5
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)3.3
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)0
Duration of Response (DoR) Median RECIST 1.1 Criteria Secondary · Through study period, assessed up to 4 years

Defined as the time from the first PR/CR to disease progression or the last tumor assessment. DoR will be determined based on tumour assessment RECIST 1.1 criteria Per RECIST for target lesions, CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For non-target lesions, CR: Disappearance of all non-target lesions.

GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)19.32.7 – 40.0
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)28.020.7 – 47.1
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)5.70.0 – 41.7
Duration of Response (DoR) Median irRECIST Criteria Secondary · Through study period, assessed up to 4 years

Defined as the time from the first PR/CR to disease progression or the last tumor assessment. DoR will be determined based on tumour assessment according to irRECIST criteria

GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)19.32.7 – 40.0
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)28.020.7 – 47.1
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)5.70.0 – 41.7
Percentage of Participants With Treatment-Related Adverse Events (TRAEs) Secondary · Throughout the study period, from start treatment up 90 days after the last dose, up to 5 years.

Percentage of patients who presented adverse events related with study treatment throughout the study period, Toxicity will be evaluated according NCI CTCAE v 5.0 criteria. AEs and SAEs will be collected from the time of the patient signing the informed consent form until the follow-up period is completed (90 days after the last dose of durvalumab ± tremelimumab).

AE related to durvalumab
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)67.6
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)86.7
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)75.9
AE related to tremelimumab
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)62.2
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)83.3
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)75.0
AE related to to both treatments (Durvalumab/Tremelimumab)
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)62.2
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)83.3
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)72.2
Toxicity grade >=3
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)13.5
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)26.7
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)16.7
SAE
GroupValue95% CI
COHORT 1: Advanced, Radioiodine-refractory Differentiated Thyroid Carcinoma (DTC)70.3
COHORT 2: Advanced Medullary Thyroid Carcinoma (MTC)60.0
COHORT 3: Advanced Anaplastic Thyroid Carcinoma (ATC)66.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events are collected up to 90 days after the end of treatment, up to 5 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

COHORT 1: Durvalumab + Tremelimumab
Serious: 26/37 (70%)
Deaths: 11/37
COHORT 1: Durvalumab Monotherapy
Serious: 0/26 (0%)
Deaths: 18/26
COHORT 2: Durvalumab + Tremelimumab
Serious: 18/30 (60%)
Deaths: 1/30
COHORT 2: Durvalumab Monotherapy
Serious: 0/25 (0%)
Deaths: 10/25
COHORT 3: Durvalumab + Tremelimumab
Serious: 8/12 (67%)
Deaths: 2/12
COHORT 3: Durvalumab Monotherapy
Serious: 0/10 (0%)
Deaths: 7/10

Serious adverse events (57 terms)

ReactionSystemCOHORT 1: Durvalumab + Tre…COHORT 1: Durvalumab Monot…COHORT 2: Durvalumab + Tre…COHORT 2: Durvalumab Monot…COHORT 3: Durvalumab + Tre…COHORT 3: Durvalumab Monot…
DiarrheaGeneral disorders
PruritusSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
MyositisMusculoskeletal and connective tissue disorders
DyspneaRespiratory, thoracic and mediastinal disorders
FractureInjury, poisoning and procedural complications
FatigueGeneral disorders
Lung infectionRespiratory, thoracic and mediastinal disorders
COVID-19Infections and infestations
ColitisGastrointestinal disorders
Alanine aminotransferas e increasedInvestigations
Aspartate aminotransferas e increasedInfections and infestations
ArthritisMusculoskeletal and connective tissue disorders
EncephalitisInfections and infestations
DysphagiaGastrointestinal disorders
Abdominal painGastrointestinal disorders
Lumbar painGeneral disorders
Disease progressionGeneral disorders
Cognitive disturbanceNervous system disorders
HypokalemiaMetabolism and nutrition disorders
Multi-organ failureGeneral disorders
Enterocolitis infectiousGastrointestinal disorders
DiverticulitisGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
Other, specify: Tubulointerstitial nephritisRenal and urinary disorders
Other adverse events (35 terms — click to expand)

ReactionSystemCOHORT 1: Durvalumab + Tre…COHORT 1: Durvalumab Monot…COHORT 2: Durvalumab + Tre…COHORT 2: Durvalumab Monot…COHORT 3: Durvalumab + Tre…COHORT 3: Durvalumab Monot…
FatigueGeneral disorders
PruritusSkin and subcutaneous tissue disorders
DiarrheaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
AnemiaGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
DysphagiaGastrointestinal disorders
FeverGeneral disorders
Neck painGeneral disorders
Dry skinSkin and subcutaneous tissue disorders
Lipase increasedInvestigations
Mucositis oralGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
GGT increasedInvestigations
Bone painMusculoskeletal and connective tissue disorders
Creatinine increasedInvestigations
Urinary tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
CoughGeneral disorders
Edema limbsGeneral disorders
PainGeneral disorders
COVID-19Infections and infestations
HypercalcemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
Serum amylase increasedInvestigations
InsomniaPsychiatric disorders
NauseaGastrointestinal disorders
DermatitisSkin and subcutaneous tissue disorders
Upper respiratory infectionInfections and infestations

Most-reported serious reactions: Diarrhea, Pruritus, Rash maculo-papular, Myositis, Dyspnea, Fracture, Fatigue, Lung infection.

Data from ClinicalTrials.gov NCT03753919 adverse events section.

Sponsor's own description

This is a prospective, multi-centre, open label, stratified, exploratory phase II study evaluating the efficacy and safety of durvalumab plus tremelimumab in different cohorts of patients with thyroid cancers.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The Immune Landscape of Thyroid Cancer in the Context of Immune Checkpoint Inhibition.
    Varricchi G, Loffredo S, Marone G, Modestino L, et al · · 2019 · cited 78× · PMID 31412566 · DOI 10.3390/ijms20163934
  2. Perspectives on the Treatment of Advanced Thyroid Cancer: Approved Therapies, Resistance Mechanisms, and Future Directions.
    Porter A, Wong DJ. · · 2020 · cited 44× · PMID 33569345 · DOI 10.3389/fonc.2020.592202
  3. What is the status of immunotherapy in thyroid neoplasms?
    Garcia-Alvarez A, Hernando J, Carmona-Alonso A, Capdevila J. · · 2022 · cited 30× · PMID 35992118 · DOI 10.3389/fendo.2022.929091
  4. Metastatic medullary thyroid carcinoma: a new way forward.
    Angelousi A, Hayes AR, Chatzellis E, Kaltsas GA, et al · · 2022 · cited 30× · PMID 35521769 · DOI 10.1530/erc-21-0368
  5. From biomarkers to therapeutic targets: the promise of PD-L1 in thyroid autoimmunity and cancer.
    D'Andréa G, Lassalle S, Guevara N, Mograbi B, et al · · 2021 · cited 30× · PMID 33391536 · DOI 10.7150/thno.50333
  6. Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses.
    Laetitia G, Sven S, Fabrice J. · · 2020 · cited 26× · PMID 32235612 · DOI 10.3390/cells9040830
  7. Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance.
    Hamidi S, Hofmann MC, Iyer PC, Cabanillas ME, et al · · 2023 · cited 25× · PMID 37435488 · DOI 10.3389/fendo.2023.1176731
  8. Tumor-associated macrophages as a potential therapeutic target in thyroid cancers.
    Zhu L, Li XJ, Gangadaran P, Jing X, et al · · 2023 · cited 19× · PMID 37796300 · DOI 10.1007/s00262-023-03549-6

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