H&N NEO-COMBAT XL: Neoadjuvant XL-092 (Zanzalintinib) and Pembrolizumab (Keytruda) in Surgically Resectable, HPV Negative Oral Cavity Squamous Cell Carcinoma (OCSCC)

NCT07484139 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LCCC2517
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Oral Cavity Squamous Cell Carcinoma; Head and Neck Cancer

Keywords

surgically resectable; neoadjuvant treatment; XL092; pembrolizumab; pathologic response; HPV negative

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 66 days

Secondary Outcomes (5)

• Neoadjuvant Adverse Events

  Up to 66 days

• Events Free Survival (EFS)

  Up to 15 months

• Objective response rate (ORR)

  Up to 15 months

• Time to surgery

  Up to 66 days

• Overall survival (OS)

  Up to 15 months

Study Arms (1)

Locally advanced oral cavity squamous cell carcinoma

EXPERIMENTAL

Locally advanced oral cavity squamous cell carcinoma (OCSCC) with surgically resectable disease.

Drug: XL092; Drug: Pembrolizumab

Interventions

XL092 DRUG

60 mg oral once a day

Locally advanced oral cavity squamous cell carcinoma

Pembrolizumab DRUG

200 mg intravenous for 30 minutes in every 21 days for

Locally advanced oral cavity squamous cell carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ECOG or Karnofsky Performance Status of 0-1
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) within 30 days prior to treatment .

You may not qualify if:

• 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).

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Exelixis: collaborator

Study Sites (3)

Emory University

Atlanta, Georgia, 30322, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Study Officials

• Siddharth Sheth, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rose Hall

CONTACT

919-984-0000; rose_hall@med.unc.edu

Shamina Williams

CONTACT

919-984-0000; shamina_williams@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: March 19, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: May 8, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)