XL092 + Cemiplimab for Thyroid Cancer

(NEO-COMBATXL Trial)

Recruiting at 1 trial location

Overseen By Rose Hall

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Immune modulators, Kinase inhibitors

Disqualifiers: Pregnant, Breastfeeding, Autoimmune disease, Allergic reactions, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not clearly specify if you need to stop your current medications. However, if you are on medications that are prohibited by the trial, you may need to stop or switch them at least 7 days before starting the trial treatment.

What data supports the effectiveness of the drug combination XL092 and Cemiplimab for thyroid cancer?

Cemiplimab has shown effectiveness in treating other types of cancer, such as cervical and lung cancer, by blocking a protein that helps cancer cells hide from the immune system. This suggests it might also help in treating thyroid cancer when combined with other treatments. ^{1 2 3 4 5}

Is the combination of XL092 and Cemiplimab safe for humans?

Cemiplimab has been studied in various cancers and generally shows a safety profile similar to other treatments targeting the PD-1 receptor, with low rates of treatment discontinuation and death. While specific data on XL092 is not provided, cemiplimab's safety in different conditions suggests it is generally safe in humans. ^{2 6 7 8 9}

How is the drug XL092 + Cemiplimab different from other thyroid cancer treatments?

The combination of XL092 and Cemiplimab is unique because it targets thyroid cancer through a novel approach, potentially involving immune system modulation and specific cancer pathways, unlike traditional treatments that may focus solely on inhibiting specific mutations like BRAFV600E. This combination could offer a new option for patients who do not respond well to existing therapies. ^{1 10 11 12 13}

What is the purpose of this trial?

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).

Research Team

Siddharth Sheth, DO MPH

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults over 18 with anaplastic thyroid cancer that doesn't have the BRAF V600E mutation. Participants must be able to follow study procedures, provide consent, and not be allergic to antibody treatments. They can't join if they're pregnant, breastfeeding, have had certain prior treatments for cancer or significant autoimmune disease requiring immunosuppression.

Inclusion Criteria

Written informed consent obtained to participate in the study and HIPAA authorization for the release of personal health information

Subjects willing and able to comply with study procedures based on the judgment of the investigator

I am willing to undergo a biopsy before treatment and during surgery if needed.

Exclusion Criteria

Subject history of documented allergic reactions or acute hypersensitivity reactions attributed to antibody treatments

Participation in another clinical study with an investigational product during the last 3 weeks

Pregnant or breastfeeding (Note: breast milk cannot be stored for future use while the mother is being treated on the study)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant XL092 and cemiplimab prior to surgical resection

10 weeks

Surgery

Participants undergo surgical resection following neoadjuvant therapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Cemiplimab
• XL092

Trial Overview The study tests a combination of two drugs: XL092 and Cemiplimab before surgery in patients with specific thyroid cancer. It aims to assess the safety and how feasible this treatment approach is before removing the tumor surgically.

Participant Groups

Group I: neoadjuvant XL092 and cemiplimab Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

In a study of 103 patients with advanced thyroid cancer, pembrolizumab showed a modest objective response rate of 6.8%, with a median duration of response lasting 18.4 months, indicating some effectiveness in this challenging cancer type.

The treatment was associated with manageable toxicity, as 69.9% of patients experienced treatment-related adverse events, but only 14.6% had severe (grade 3-5) reactions, suggesting that pembrolizumab can be safely administered to this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. Oh, DY., Algazi, A., Capdevila, J., et al.[2023]

In a phase 3 study involving 710 patients with advanced non-small-cell lung cancer and high PD-L1 expression, cemiplimab significantly improved overall survival (not reached) and progression-free survival (8.2 months) compared to chemotherapy (14.2 months).

Cemiplimab also demonstrated a better safety profile, with fewer grade 3-4 treatment-emergent adverse events (28%) compared to chemotherapy (39%), making it a promising first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Sezer, A., Kilickap, S., Gümüş, M., et al.[2022]

The updated population pharmacokinetic model for cemiplimab, based on data from 1062 patients, demonstrated improved stability and robustness, successfully validating its pharmacokinetics in patients with recurrent or metastatic cervical cancer.

Despite the improved model, the analysis revealed no significant exposure-response relationships for efficacy (overall survival, progression-free survival, duration of response, objective response rate) or safety (immune-related adverse events), indicating that higher drug exposure did not correlate with better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics modeling and exposure-response analyses of cemiplimab in patients with recurrent or metastatic cervical cancer. Nguyen, JH., Epling, D., Dolphin, N., et al.[2023]

Cemiplimab is the first FDA-approved treatment for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, demonstrating rapid and substantial antitumor efficacy in phase II clinical trials.

The treatment has an acceptable safety profile, with low rates of treatment discontinuation (7%) and death (3%), although current recommendations are based mainly on phase II data due to the lack of an approved comparator agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. Naik, PP.[2022]

In a phase Ib trial involving 22 patients with advanced differentiated thyroid cancer, pembrolizumab showed a manageable safety profile, with 82% experiencing treatment-related adverse events, primarily diarrhea and fatigue, but no treatment-related deaths.

The treatment demonstrated limited efficacy, with an objective response rate of 9% and a median progression-free survival of 7 months, indicating that while some patients may benefit, further research is needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer. Mehnert, JM., Varga, A., Brose, MS., et al.[2020]

PLX4032, a BRAFV600E-specific inhibitor, effectively reduces the growth of BRAFV600E-positive papillary thyroid cancer cells while having the opposite effect on normal BRAF-wild-type thyroid cells, indicating its targeted efficacy.

The anti-proliferative effects of PLX4032 in BRAF-mutated cells are linked to its ability to inhibit key signaling molecules in the MAPK pathway, suggesting a potential for combination therapies in treating thyroid cancer with this mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disruption of mutated BRAF signaling modulates thyroid cancer phenotype. Hanly, EK., Rajoria, S., Darzynkiewicz, Z., et al.[2021]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

IL6/STAT3 axis mediates resistance to BRAF inhibitors in thyroid carcinoma cells. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Cemiplimab for Orbital Squamous Cell Carcinoma in 11 Cases. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics modeling and exposure-response analyses of cemiplimab in patients with recurrent or metastatic cervical cancer. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic characteristics of cemiplimab in patients with advanced malignancies. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Disruption of mutated BRAF signaling modulates thyroid cancer phenotype. [2021]

11. England pubmed.ncbi.nlm.nih.gov

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes. [2022]

12. Korea (South) pubmed.ncbi.nlm.nih.gov

Selective inhibition of V600E-mutant BRAF gene induces apoptosis in thyroid carcinoma cell lines. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Vemurafenib may overcome TNF-related apoptosis-inducing ligand (TRAIL) resistance in anaplastic thyroid cancer cells. [2021]