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.
Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
Age ≥ 18 years at the time of consent.
Tumors must have PD-L1 Combined Positive Score (CPS) ≥ 1.
Known HPV-positive cancer
Active infection requiring systemic therapy.
Prior treatment with XL-092
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Single group
XL092
Drug60 mg oral once a day
Pembrolizumab
Drug200 mg intravenous for 30 minutes in every 21 days for
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.
Neoadjuvant Adverse Events
Safety will be defined as the rate of treatment emergent adverse events with neoadjuvant XL-092 and pembrolizumab (CTCAE v5.0).
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.
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 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.
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UNC Lineberger Comprehensive Cancer Center
Lead sponsor
Exelixis
Collaborator
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