This is a multicenter, single arm Phase 2B study in subjects with locally advanced oral cavity squamous cell carcinoma (OCSCC) with surgically resectable disease. The study will assess the combination of neoadjuvant XL092 and pembrolizumab for safety and improvement of pathologic response rates compared to historical standard of care with perioperative pembrolizumab. The primary objective is to estimate the pathologic response rate defined as either pathological complete response (pCR), which is the absence of residual viable tumor, or major pathologic response (MPR), which is \<10% of residual tumor following the completion of neoadjuvant therapy and surgery. The study will be conducted in two stages. Per Simon's Stage 1, 11 patients will be enrolled. Simon Stage 2 will be gated on multiple factors. If ≥2 pathologic response is observed (pCR or MPR), the trial will proceed with cohort expansion and enroll an additional 15 patients for a total of 26 patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
60 mg oral once a day
200 mg intravenous for 30 minutes in every 21 days for
Emory University
Atlanta, Georgia, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Rate of pathologic response
Rate of pathologic response, assessed following surgery, will be defined as either pathological complete response (pCR), which is the absence of residual viable tumor or major pathological response (MPR), which is \<10% residual tumor.
Time frame: Up to 66 days
Neoadjuvant Adverse Events
Safety will be defined as the rate of treatment emergent adverse events with neoadjuvant XL-092 and pembrolizumab (CTCAE v5.0).
Time frame: Up to 66 days
Events Free Survival (EFS)
EFS will be defined as the time from 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 Radiographic response will be measured according to Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). RECIST indicating if subject experienced a 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: Up to 15 months
Objective response rate (ORR)
ORR following neoadjuvant therapy: an objective response will be classified per the Radiographic response will be measured according to Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1) if a partial or complete response is observed. RECIST indicating if subject experienced a 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: Up to 15 months
Time to surgery
Time to surgery: defined as the time from completion of neoadjuvant therapy to date of surgery. Individuals who do not receive surgery due to progressive disease, non-TEAE death or individuals who experience surgery delays due to toxicity will not be counted.
Time frame: Up to 66 days
Overall survival (OS)
OS is defined as the time from time of first treatment to death due to any cause.
Time frame: Up to 15 months
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