NCT04731740

Pembrolizumab and Lenvatinib/Chemotherapy for Poorly Differentiated/Anaplastic Thyroid Cancer

Pembrolizumab in Combination With Standard 1st Line Therapy (Lenvatinib / Chemotherapy) for Locally Advanced or Metastatic Poorly Differentiated or Anaplastic Thyroid Cancer

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Saint Petersburg State University, Russia · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aim of the study is to evaluate the efficacy of the combination of lenvatinib with pembrolizumab, and to establish a safe and effective systemic treatment regimen for patients with metastatic anaplastic thyroid cancer (ATC) / poorly differentiated thyroid cancer (PDTC). Lenvatinib is an anti-angiogenic and antiproliferative drug used in differentiated thyroid cancer. It blocks proliferative genes such as RET and PDGFR and further inhibits major proliferation pathways such as VEGF receptor signaling and FGFR1-4. Pembrolizumab is an immune checkpoint inhibitor that targets PD-1 located on lymphocytes. The response to pembrolizumab treatment is associated, among other things, with increased expression of PD-L1, as well as with the frequency of somatic mutations in the respective tumors. Patients with ATC / PDTC show high expression of PD-L1.

Detailed description

Primary endpoint 1. Objective Response Ratio (ORR) \[Time frame: prior to study completion, average 3 years\] * Evaluate the effectiveness of a combination of a PD-1 inhibitor (pembrolizumab) with a multikinase inhibitor (lenvatinib) using an objective response rate (ORR) in poorly differentiated or anaplastic thyroid cancer at 12 weeks and 24 weeks after starting treatment. * Evaluate the efficacy of the investigator's choice of chemotherapy plus PD-1 inhibitor (pembrolizumab) using an objective response rate (ORR) in poorly differentiated or anaplastic thyroid cancer at 12 weeks and 24 weeks after initiation of treatment. Includes patients with a confirmed partial (PR) and complete response (CR) as the best response according to RECIST v 1.1. 2. Overall survival at 6 months in the pembrolizumab and lenvatinib cohort \[Time frame: 6 months\] Secondary endpoints 1. Safety Profile (Number / Severity of Serious Adverse Events, SAEs) \[Timeline: SAEs will be reported in the clinical trial within 6 months of the end of the study\] 2. Duration of Response (DoR) \[Time frame: from date of first documented clinical response (PR, CR) to date of first documented progression, date of death from any cause or patient failure, whichever comes first, is estimated to be 36 months\] 3. Progression-Free Survival (PFS) \[Time frame: from date of enrollment to date of first documented progression, date of death from any cause or patient failure, whichever is earlier, up to 36 months\] 4. Overall Survival (OS) \[Time frame: from the date of enrollment to the date of death from any cause or patient failure, whichever comes first, estimated up to 36 months\] Study design Prospective interventional two-cohort non-comparative single-center study.

Conditions

• Metastatic Thyroid Gland Carcinoma
• Poorly Differentiated Thyroid Gland Carcinoma
• Thyroid Gland Anaplastic Carcinoma by AJCC V8 Stage

Interventions

Type	Name	Description
DRUG	Lenvatinib	PO
BIOLOGICAL	Pembrolizumab	IV
DRUG	Chemotherapy	Investigators' choice

Timeline

• Start date: 2020-12-28
• Primary completion: 2023-12-28
• Completion: 2023-12-28
• First posted: 2021-02-01
• Last updated: 2024-03-25

Locations

1 site across 1 country: Russia