XL092 and Cemiplimab in BRAF WT Thyroid Cancer

NCT06902376 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LCCC2255
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Anaplastic Thyroid Cancer; Thyroid Cancer; BRAF Mutation-Related Tumors

Keywords

neoadjuvant chemotherapy; neoadjuvant immunotherapy; standard of care; BRAF V600E-WT ATC; XL092; cemiplimab; receptor tyrosine kinase inhibitor

Outcome Measures

Primary Outcomes (2)

• Complete 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.

  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.

  Up to 2 years

Secondary Outcomes (6)

• Objective response rate (ORR)

  10 weeks

• Time to surgery

  12 weeks

• The rate of pathologic response

  12 weeks

• Conversion rate from unresectable to resectable disease

  12 weeks

• Event free survival (EFS)

  Up to 5 years

Study Arms (1)

neoadjuvant XL092 and cemiplimab

EXPERIMENTAL

Subjects with BRAFV600E wild type (WT) anaplastic thyroid cancer (ATC) who are scheduled to undergo surgical resection as part of their standard of care will receive neoadjuvant XL092 and cemiplimab. Adjuvant therapy may be indicated based on surgical pathology.

Biological: Cemiplimab; Drug: XL092

Interventions

Cemiplimab BIOLOGICAL

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.

neoadjuvant XL092 and cemiplimab

XL092 DRUG

XL092 will be administered at a dose of 60mg PO daily for 8 weeks (weeks 1-8)

neoadjuvant XL092 and cemiplimab

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 was obtained to participate in the study and HIPAA authorization for the release of personal health information.
• Subjects are willing and able to comply with study procedures based on the judgment of the investigator.
• Age ≥ 18 years at the time of consent.
• the Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Pathologic findings supporting the clinical impression of anaplastic thyroid cancer. Terminology consistent or suggestive of diagnosis may include the following: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present.
• Subject is willing to have a fresh biopsy at least 3 days prior to neoadjuvant therapy if archival tissue is unavailable. Also willing to have a biopsy at the time of SOC surgery, if applicable.
• Must have BRAF V600E mutation-negative tumor, as determined by BRAF V600E immunohistochemistry on tumor tissue or genetic/molecular testing of the tumor.

You may not qualify if:

• Pregnant or breastfeeding (Note: breast milk cannot be stored for future use while the mother is being treated on the study). Females should not breastfeed while receiving study treatment and for 1 month from the last dose of XL092.
• Patients who have had prior exposure to any immune modulating agents or any type of small molecule kinase inhibitor (including investigational agents) and have documented disease progression on these agents will not be eligible.
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments (i.e., with use of disease modifying agents, corticosteroids (\>10 mg of prednisone or equivalent) or immunosuppressive drugs) which may suggest risk of immune-mediated Adverse Events.
• Subject history of documented allergic reactions or acute hypersensitivity reactions attributed to antibody treatments.
• Subject is receiving prohibited medications or treatments as listed in the protocol that cannot be discontinued/replaced by an alternative therapy within 7 days of initiating treatment.
• Participation in another clinical study with an investigational product during the last 3 weeks.

Sponsors & Collaborators

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

Study Sites (2)

Dana Farber/Harvard Cancer Center

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• UNC Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Siddharth Sheth, DO MPH

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rose Hall

CONTACT

1-(919) 966-0808; rose_hall@med.unc.edu

Lori Stravers

CONTACT

1-(919) 966-4432; lori_stravers@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: March 30, 2025
• Study Start: June 3, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: November 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)