This multicenter study examines the safety and feasibility of the combination of neoadjuvant XL092 and cemiplimab prior to surgical resection in participants with wild-type (WT) anaplastic thyroid cancer (ATC) that has a BRAF mutation (BRAF V600E).
This study includes subjects with BRAFV600E wild type (WT) anaplastic thyroid cancer (ATC) who are scheduled to undergo surgical resection as part of their standard of care. The study hypothesizes that the combination of neoadjuvant XL092 and cemiplimab will be safe and feasible prior to surgical resection in participants with BRAF V600E-WT ATC. Anaplastic thyroid cancer (ATC) is a highly aggressive and fatal malignancy. For patients with BRAF V600E-wildtype ATC, chemotherapy, whether as a single agent or in combination, remains the standard treatment despite its low response rates. Studies have shown that while immunotherapy (IO) and receptor tyrosine kinase inhibitor (TKI) monotherapy are safe for these patients, their efficacy as single agents is limited. This study addresses a significant unmet need and is based on the strong synergy observed between IO and TKI in clinical studies of other cancers. It includes subjects with BRAF V600E-wildtype ATC who are scheduled for surgical resection as part of their standard care. The study hypothesizes that the combination of neoadjuvant XL092 and cemiplimab will be safe and feasible before surgical resection in these patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Cemiplimab will be administered at a dose of 350mg intravenous over 30 minutes every 3 weeks for 3 cycles (cycle length is 21 days) at weeks 1, 4, and 7.
XL092 will be administered at a dose of 60mg PO daily for 8 weeks (weeks 1-8)
Dana Farber/Harvard Cancer Center
Boston, Massachusetts, United States
NOT_YET_RECRUITINGUniversity of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
RECRUITINGComplete gross resection
Complete gross resection (CGR) is defined as the proportion of patients who undergo successful thyroidectomy with negative (R0) or microscopically positive (R1) surgical margins.
Time frame: 12 weeks
Non-hematologic treatment related adverse events (TRAEs)
Non-hematologic treatment related adverse events (TRAEs) with neoadjuvant and maintenance XL092 and cemiplimab will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI- CTCAE) v5.0.
Time frame: Up to 2 years
Objective response rate (ORR)
Objective response rate (ORR) following neoadjuvant therapy prior to surgery as defined as a partial or complete response per Radiographic response will be measured by RECIST, 1.1 criteria. Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 10 weeks
Time to surgery
Time to surgery following completion of neoadjuvant XL092 and cemiplimab will be defined as the time from completion of neoadjuvant therapy to date of surgery. Participants who do not receive surgery due to progressive disease or non-treatment-related adverse events death will not be counted.
Time frame: 12 weeks
The rate of pathologic response
The rate of pathologic response will be defined as either a pathological complete response (pCR), which is the absence of a residual viable tumor or a major pathological response (MPR), which is \< 10% residual tumor following neoadjuvant therapy and surgery.
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Time frame: 12 weeks
Conversion rate from unresectable to resectable disease
Conversion rate from unresectable to resectable disease will be defined as the number of subjects with unresectable disease at the time of screening who are deemed to have resectable disease at the completion of neoadjuvant therapy.
Time frame: 12 weeks
Event free survival (EFS)
Event free survival (EFS) will be defined as the time of first treatment to an event which may include disease progression, discontinuation of the treatment for any reason, or death from any cause, where disease progression will be determined based on RECIST 1.1 criteria. If a patient has no events, they will be censored at the last known alive date. Complete Response (CR), the disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Up to 5 years
Overall survival (OS)
Overall survival (OS) of participants receiving neoadjuvant XL092 and cemiplimab will be defined as the time from the date of first treatment to death.
Time frame: Up to 5 years