Abstract 4155
Background
Preliminary studies have suggested that the activity of anti-PD-1 immune check-point inhibitors in thyroid cancer is low. However, we hypothesize that combining CTLA-4 and PD-L1 clockade could have a higher effet in the setting of refractory thyroid carcinomas, in which the process of de-differentiation and evasive tumor resistance are associated with increased mutational load.
Trial design
This prospective, multi-center, open-label, phase II study will evaluate the efficacy and safety of Durvalumab plus Tremelimumab within three parallel cohorts: differentiated (DTC), medullary (MTC), and anaplastic (ATC) thyroid cancers. Pts will receive Durvalumab 1500mg plus Tremelimumab 75mg every 4 weeks for up to 4 cycles followed by Durvalumab until PD, unacceptable toxicity or patients’ decision. Main end point in cohorts 1 and 2 is progression-free survival (PFS). We hypothesize an increase of 6-months from 25% in historical cohorts up to 45%. A Simon two-stage design will be employed with 17 pts per cohort in the first phase. If 5/17 pts in each cohort (DTC and MTC) are event free and without unacceptable toxicity at 6 months in the first stage, 19 additional pts will be reruited up to 36 pts per cohort. For cohort 3 (ATC), we hypothesize an improvement the probability of being alive at 6 months from 5% in historical cohorts up to 35%. 12 pts are needed in this cohort. Secondary objectives include overall response rate by irRECIST and RECIST, duration of response, safety profile and biomarkers. The main inclusion criteria for the three cohorts are: Cohort 1: Pts with locally advanced or metastatic DTC after PD on multikinase inhibitors (MKIs). Cohort 2: Pts with locally advanced or metastatic MTC after PD to MKIs. Cohort 3: Pts with ATC irrespective of prior therapy. No prior treatment with immune checkpoint inhibitors is allowed. The study is currently recruiting pts with 6 out of 46 planned pts enrolled at time of submission.
Clinical trial identification
EudraCT: 2018-001066-42.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Spanish Group of Neuroendocrine and Endocrine Tumors (GETNE).
Disclosure
J. Hernando Cubero: Speaker Bureau / Expert testimony: Eisai, Ipsen, Roche, Angelini; Travel / Accommodation / Expenses: Ipsen, Novartis, AAA, Roche, AstraZeneca, Eisai. M. Taberna Sanz: Advisory / Consultancy: Merck, Nanobiotics, AstraZeneca, MSD and Bristol Myers..A. Carmona Bayonas: Speaker Bureau / Expert testimony: Novartis, Ipsen; Travel / Accommodation / Expenses: Novartis, Ipsen. L. Iglesias: Advisory / Consultancy: Merck Serono, MSD, BMS, Bayer and Sanofi; Speaker Bureau / Expert testimony: Merck Serono, MSD, AstraZeneca and BMS..E. Grande: Advisory / Consultancy: Pfizer, Ipsen, BMS, Eisai, Roche, MSD, Sanofi, Adacap, Novartis, EUSA Pharma, Pierre Fabre, Lexicon, Celgene; Research grant / Funding (institution): MSD, Roche. J.M. Trigo Perez: Advisory / Consultancy: BMS, MSD, Behringer, GSK; Speaker Bureau / Expert testimony: AstraZeneca, Bayer, Roche; Travel / Accommodation / Expenses: MSD, BMS. T. Alonso Gordoa: Advisory / Consultancy: BMS, MSD, Roche, Astellas, IPSEN, Sanofi; Speaker Bureau / Expert testimony: Pfizer, Ipsen, Janssen, Astellas, Novartis.; Research grant / Funding (self): Roche; Travel / Accommodation / Expenses: Pfizer, Sanofi. J. Lavernia: Speaker Bureau / Expert testimony: Roche, BMS, Sun Pharma, Sanofi and Merck Serono. J. Capdevila: Advisory / Consultancy: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, AAA, Amgen, Sanofi, Merck; Honoraria (institution): Eisai, Novartis, Ipsen, AstraZeneca, Pfizer, AAA. All other authors have declared no conflicts of interest.
Resources from the same session
1933 - A national comparative effectiveness study to assess definitive chemoradiation regimens in proximal oesophageal squamous cell cancer
Presenter: Judith de Vos-Geelen
Session: Poster Display session 2
Resources:
Abstract
2860 - Prognostic value of metabolic response assessed by 18FDG-PET after induction chemotherapy and after chemoradiotherapy (CRT) in localized esophageal squamous cell carcinoma (ESCC) patients (pts) receiving definite CRT (dCRT)
Presenter: Yeonghak Bang
Session: Poster Display session 2
Resources:
Abstract
3881 - Comprehensive genomic profiling of early-stage esophageal squamous cell carcinoma
Presenter: Jing Zuo
Session: Poster Display session 2
Resources:
Abstract
3944 - A novel nomogram and risk classification system predicting radiation pneumonitis in patients with esophageal cancer receiving radiotherapy
Presenter: Lu Wang
Session: Poster Display session 2
Resources:
Abstract
1956 - Drinking alcohol, smoking, multiple dysplastic lesions and the risk of field cancerization of squamous cell carcinoma in the esophagus and head and neck region
Presenter: Chikatoshi Katada
Session: Poster Display session 2
Resources:
Abstract
2144 - Neoadjuvant chemotherapy can eliminate the negative impact of postoperative infectious complications on recurrence in patients with esophageal cancer
Presenter: Kazuki Kano
Session: Poster Display session 2
Resources:
Abstract
2403 - Comparison of chemoradiotherapy (CRT) followed by consolidation with cisplatin and 5-fluorouracil (CF) versus definitive CRT with carboplatin and paclitaxel (CP) in esophageal cancer
Presenter: Marcelle Cesca
Session: Poster Display session 2
Resources:
Abstract
3247 - Paclitaxel in Combination with Cisplatin and 5-fluorouracil(TPF) Induction Chemotherapy for Locally Advanced Borderline-resectable Esophageal Squamous cell Carcinoma: A Phase II Clinical Trial
Presenter: Yuhong Li
Session: Poster Display session 2
Resources:
Abstract
4293 - Prognosis of esophageal squamous cell carcinoma based on local immunity evaluation
Presenter: Elena Zlatnik
Session: Poster Display session 2
Resources:
Abstract
5419 - Impact of Sarcopenia and adiposity in survival of metastatic esophageal cancer (MEC)
Presenter: Aline Fares
Session: Poster Display session 2
Resources:
Abstract