1645O - Durvalumab (D) plus tremelimumab (T) for the treatment of patients with progressive, refractory advanced thyroid carcinoma: The DUTHY (GETNE-T1812) trial

Background

Targeting PD-L1 has proven limited efficacy in advanced thyroid cancer patients (pts). Dual targeting of PD-L1 and CTLA-4 could improve the efficacy of immunotherapy.

Methods

Pts with advanced thyroid cancers were recruited in three cohorts (C1-3): differentiated thyroid cancer (DTC, C1), medullary thyroid cancer (MTC, C2), and anaplastic thyroid cancer (ATC, C3). Pts in C1 and C2 were included after disease progression on standard systemic therapy and C3 regardless of prior therapy. No prior immunotherapy was allowed. Pts received D 1500 mg and T 75 mg every 4 weeks, up to 4 cycles, followed by durvalumab monotherapy until confirmed disease progression, or unacceptable toxicity. Primary objective was 6-month (m) PFS rate for C1-2 and 6-m overall survival (OS) rate for C3. Secondary objectives included safety and efficacy in terms of Objective Response Rate (ORR), median PFS and OS. The expected accrual was 37/37/12 pts respectively for C1-3.

Results

From April 2019, 68 pts were enrolled; 37/19/12 in C1-3. C1 and C3 completed accrual, C2 completed the 1st stage and 2nd stage is open. Median age was 66 years; 39 (57.4%) were female. Pts received a median of 2/2/0 previous treatment lines for C1-3 respectively. Surgery of the primary tumor was performed in 35 (94.6%) / 16 (84.2%) / 2 (16.7%) pts in C1-3 respectively. The median follow-up was 12.2 m (range: 0.2-34.5) / 16.8 m (range: 1.4-32.9) / 11.5 m (range: 1.5-29.9), with a 6-m PFS rate of 32.4% / 37.5% / 33.3%, and median PFS of 5.3 m (95% CI: 2.7-6.5) / 5.3 m (95% CI: 2.8-NR) / and 4 m (95% CI: 2.2-NR), for C1-3 respectively. The 6-m OS rate was 70.3% / 93.8% / 65.6%, with a median OS of 12.5 m (95% CI: 9.4-NR) / NR / 13.8 m (95% CI: 5.7-NR), for C1-3 respectively. The ORR according to RECIST 1.1 was 8.1% / 15.8% / 33.3% for C1-3 respectively. In C3, the ORR was 50% in PD-L1 positive pts. In total 47 (71.2%) pts experienced toxicities, with 10 (15.2%) pts experiencing grade ≥3 toxicities. The toxicity was similar to previous trials with DT.

Conclusions

D+T was tolerable and showed promising activity in heavily pretreated advanced DTC and MTC. In ATC cohort, D+T demonstrated significant and clinically meaningful efficacy with prolonged OS, granting further research.

Clinical trial identification

EudraCT 2018-001066-42; NCT03753919.

Editorial acknowledgement

We acknowledge MFAR Clinical Research staff for their assistance in the development of this abstract.

Legal entity responsible for the study

Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE).

Funding

GETNE though industry partner AstraZeneca.

Disclosure

J. Capdevila Castillon: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Hudchinson Pharma, ITM, Advanz, Merck Serono, Esteve; Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Hudchinson Pharma, ITM, Advanz, Merck Serono, Esteve; Financial Interests, Personal, Research Grant: Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications, Eisai, Amgen, Bayer; Financial Interests, Institutional, Member, Chair of the Spanish Task Force for Neuroendocrine and Endocrine Tumors Group (GETNE): GETNE; Financial Interests, Institutional, Member, Executive Committee Member of the European Neuroendocrine Tumor Society (ENETS): ENETS; Financial Interests, Institutional, Member, Treasurer and Track Chair of the reactal cancer working group of the Spanish Multidisciplinary Group of Digestive Cancers (GEMCAD): GEMCAD. M. Plana: Financial Interests, Advisory Role: Nanobiotix; Financial Interests, Other: BMS, MSD. J. Hernando: Financial Interests, Personal, Speaker’s Bureau: Eisai, Ipsen, Novartis, Adacap, Bayer, Roche, Angelini. N. Baste: Non-Financial Interests, Advisory Role: BiNTech, BMS, Eisai, Exelixis, Merck Serono; Financial Interests, Advisory Role: MSD, Roche. E. Grande: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Eusa Pharma, Ipsen, Jansen, Lilly, Merck KGA, Pfizer, Roche; Financial Interests, Personal, Advisory Role: Adacal, Bayer, Caris Life, MSD, Novartis, OncoDNA, Sanofy-Genzyme; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Ipsen, Lexicon, MTEM/Threshold, Nanostrig, Pfizer, Roche, Merck; Non-Financial Interests, Other, AD board member: ENETS. D. Lorente: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Bayer, Bristol-Myers, Janssen, MSD, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Pfizer, Sanofi. G. Marquina: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Clovis Oncology, Eisai, GSK/Tesaro, Lilly, Medicamenta, Roche; Financial Interests, Personal, Advisory Board: Clovis Oncology, GSK/Tesaro, Lilly, PharmaMar, Pfizer. A. García-Alvarez: Financial Interests, Personal, Other, Speaker, consultancy or advisory role or similar activity: Angellini, ADACAP, Eisai, Ipsen, Pfizer. T. Alonso-Gordoa: Financial Interests, Personal, Advisory Board: Ipsen, Sanofi, Bayer, Eisai, Novartis, Lilly; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, Janssen-Cilag; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Non-Financial Interests, Project Lead: Pfizer, Ipsen. All other authors have declared no conflicts of interest.