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NCT Number: NCT07484139

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

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.

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Key information

Conditions

Oral Cavity Squamous Cell Carcinoma Carcinoma Carcinoma, Squamous Cell Head and Neck Cancer Head and Neck Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Squamous Cell Carcinoma of Head and Neck

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Emory University, Atlanta, Georgia, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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 .

Exclusion criteria

  • 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).

Treatment and study plan

XL092

Drug

60 mg oral once a day

Pembrolizumab

Drug

200 mg intravenous for 30 minutes in every 21 days for

Primary outcomes

  1. Rate of pathologic response

    Time frame: Up to 66 days

    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.

Secondary outcomes

  1. Neoadjuvant Adverse Events

    Time frame: Up to 66 days

    Safety will be defined as the rate of treatment emergent adverse events with neoadjuvant XL-092 and pembrolizumab (CTCAE v5.0).

  2. Events Free Survival (EFS)

    Time frame: Up to 15 months

    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.

  3. Objective response rate (ORR)

    Time frame: Up to 15 months

    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.

  4. Time to surgery

    Time frame: Up to 66 days

    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.

  5. Overall survival (OS)

    Time frame: Up to 15 months

    OS is defined as the time from time of first treatment to death due to any cause.

Study contacts

Contact information is provided by the study sponsor or research team.

Rose Hall

CONTACT

[email protected]

919-984-0000

Shamina Williams

CONTACT

[email protected]

919-984-0000

Sponsors and collaborators

Lead sponsor

UNC Lineberger Comprehensive Cancer Center

Other

Collaborators

  • Exelixis

Registry information

Acronym: NEO COMBAT XL

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Mar 19, 2026
Registry last updated
May 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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