A multicenter, single-arm phase 2 study of surufatinib plus toripalimab for patients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer.

Dongmei Ji Fudan University Shanghai Cancer Center, Shanghai, China info_outline Dongmei Ji, Lijie Song, Ying Cheng, Weina Shen, Muyu Kuang, Jiaying Chen, Minjie Yang, Hongxia Cui, Jinghong Zhou, Haiyan Shi, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su, Qinghai Ji

Authors Dongmei Ji Fudan University Shanghai Cancer Center, Shanghai, China info_outline Dongmei Ji, Lijie Song, Ying Cheng, Weina Shen, Muyu Kuang, Jiaying Chen, Minjie Yang, Hongxia Cui, Jinghong Zhou, Haiyan Shi, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su, Qinghai Ji Organizations Fudan University Shanghai Cancer Center, Shanghai, China, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, Department of Oncology, Jilin Cancer Hospital, Changchun, China, Jilin Cancer Hospital, Changchun, China, HUTCHMED Limited, Shanghai, China, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company HUTCHMED Limited Background: For patients (pts) with radioactive iodine–refractory differentiated thyroid cancer (RAIR-DTC), there presents a considerable therapeutic challenge with poor long-term outcomes. The open-label, multi-cohort, single-arm phase 2 study was performed to evaluate surufatinib (a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) in combination with toripalimab (an anti-PD-1 antibody) in pts with RAIR-DTC. Methods: Eligible pts were with locally advanced or metastatic RAIR-DTC who were not amenable for surgery or external beam radiotherapy, with a radiologically confirmed disease progression within 12 months before treatment, and with ≥6 months since last radioiodine treatment. Enrolled pts received surufatinib 250 mg orally, QD, plus toripalimab 240 mg IV, Q3W, until disease progression or reaching the maximum treatment duration with toripalimab of 24 months, or other protocol-specified criteria. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: From March 2020 to November 2021, 15 pts were enrolled and received a median duration of 11.1 months of the combination treatment, with a median age of 61 years (range: 37-74). 9 (60%) pts were male, and 12 (80%) had papillary thyroid cancer. Of the 13 pts with PD-L1 immunochemical results, 6 pts had PD-L1 CPS ≥1%. As of 28 Dec 2022, the median follow-up duration was 22.11 months. Of the 15 pts with at least one post-baseline tumor assessment, the confirmed ORR was 33.3% (5 PRs) and DCR was 93.3%. mDoR was 8.34 months. mPFS (95%CI) was 10.91 months (4.01, NA). mOS was not reached, and 12-month OS rate was 100%. 14 (93.3%) pts had treatment-emergent adverse events (TEAEs), and 10 (66.7%) pts reported grade ≥3 TEAEs, most commonly (≥10% pts) with hypocalcemia (20%), diarrhea (20%) and hypertension (13%). There was no death due to TEAE in the study. Conclusions: Surufatinib plus toripalimab showed encouraging antitumor activity and tolerable safety profile in pts with locally advanced or metastatic RAIR-DTC. Clinical trial information: NCT04169672.

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