Triple Drug Therapy for Thyroid Cancer

Not currently recruiting at 9 trial locations

Overseen By Davic Pfister, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Dabrafenib, Trametinib

Must not be taking: Antiretrovirals, Idelalisib

Disqualifiers: Brain metastases, Lung disease, Cardiovascular risk, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a new drug, cemiplimab (an immunotherapy), to the usual treatment with dabrafenib and trametinib can effectively combat anaplastic thyroid cancer. Anaplastic thyroid cancer is a rare and aggressive cancer that rapidly grows in the thyroid gland and can spread to other body parts. The trial targets individuals with a specific change in their cancer, known as a BRAF-V600E mutation, whose cancer has either spread or cannot be completely removed through surgery. Participants must have this specific type of thyroid cancer and other health conditions that allow them to take these medicines safely. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are HIV-positive and on antiretroviral therapy, you are not eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining cemiplimab, dabrafenib, and trametinib may effectively treat anaplastic thyroid cancer. Cemiplimab has undergone testing in various situations and is considered safe for use before and after surgery in similar cancer types.

Dabrafenib and trametinib are often used together for patients with a specific genetic change (BRAF V600E) in thyroid cancer. Studies indicate they offer clear benefits, and their side effects can be managed.

Overall, these treatments appear well-tolerated, with side effects effectively managed. This makes them a promising option for those considering joining a trial for this type of cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this triple drug therapy for BRAF-mutant Anaplastic Thyroid Cancer because it combines cemiplimab, dabrafenib, and trametinib, offering a unique approach. Unlike traditional treatments, which often rely on surgery and chemotherapy, this therapy targets specific genetic mutations and pathways. Dabrafenib and trametinib work by specifically inhibiting the BRAF and MEK pathways, which are critical in the growth of cancer cells with the BRAF-V600E mutation. Cemiplimab, an immune checkpoint inhibitor, helps the immune system recognize and attack cancer cells. This combination has the potential to deliver a more tailored and effective response against this aggressive form of thyroid cancer, providing hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for anaplastic thyroid cancer?

Research shows that using dabrafenib and trametinib together yields promising results for patients with BRAF V600E-mutant anaplastic thyroid cancer. Studies report that about 81.8% of patients respond to this treatment, with cancer not worsening for an average of 7.3 months and patients living for an average of 10.3 months. In this trial, participants will receive the combination of dabrafenib and trametinib. Additionally, cemiplimab, an immune therapy, will be added to the regimen to assist when cancer progresses despite the other two drugs. Cemiplimab enhances the immune system's ability to fight cancer cells. Overall, this combination aims to be more effective than using just dabrafenib and trametinib. ^{3 4 6 7 8}

Who Is on the Research Team?

Eric Sherman, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with anaplastic thyroid cancer that has a specific BRAF-V600E mutation. It's open to those who haven't been cured by surgery, can undergo biopsies, and have measurable disease. Participants need normal heart function and organ health, must not be pregnant, agree to use contraception, and be able to take oral meds.

Inclusion Criteria

My organ and bone marrow functions are normal.

I can swallow and keep down pills.

Negative pregnancy test within 14 days of registration for women of childbearing potential

Exclusion Criteria

I have been treated with dabrafenib and trametinib.

I do not have any severe illnesses that would stop me from following the study's requirements.

I have interstitial lung disease or pneumonitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab in combination with dabrafenib and trametinib

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Dabrafenib
• Trametinib

Trial Overview The study tests if adding cemiplimab (a new drug) to standard treatment with dabrafenib and trametinib improves outcomes in anaplastic thyroid cancer. Patients will receive this combination therapy and their response will be monitored.

How Is the Trial Designed?

Group I: BRAF-mutant ATC Experimental Treatment 2 Interventions

Participants will have a diagnosis of BRAF-V600E mutant Anaplastic Thyroid Cancer

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a phase 2 trial involving 53 patients with BRAF-mutated radioactive iodine refractory differentiated thyroid cancer, both dabrafenib monotherapy and the combination of dabrafenib + trametinib showed similar objective response rates, with 42% and 48% respectively, indicating no significant advantage of the combination therapy.

The most common side effects included skin disorders and fever, but there were no treatment-related deaths, suggesting that both treatment options are relatively safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib Versus Dabrafenib + Trametinib in BRAF-Mutated Radioactive Iodine Refractory Differentiated Thyroid Cancer: Results of a Randomized, Phase 2, Open-Label Multicenter Trial. Busaidy, NL., Konda, B., Wei, L., et al.[2023]

In a phase II trial involving 16 patients with BRAF V600E-mutated anaplastic thyroid cancer, the combination of dabrafenib and trametinib showed a high overall response rate of 69%, indicating significant efficacy in a cancer type with previously limited treatment options.

The treatment was well tolerated, with common side effects including fatigue, fever, and nausea, and no new safety concerns were identified, marking a promising advancement for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. Subbiah, V., Kreitman, RJ., Wainberg, ZA., et al.[2022]

Birinapant, a drug that targets inhibitors of apoptosis proteins (IAPs), shows promise as a treatment for triple-negative breast cancer (TNBC) by enhancing the effectiveness of gemcitabine, a commonly used chemotherapy drug.

In both laboratory and mouse models, birinapant was found to activate the intrinsic apoptosis pathway, leading to increased cancer cell death when used alongside gemcitabine, suggesting a new therapeutic strategy for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Birinapant Enhances Gemcitabine's Antitumor Efficacy in Triple-Negative Breast Cancer by Inducing Intrinsic Pathway-Dependent Apoptosis. Xie, X., Lee, J., Liu, H., et al.[2022]

In a study investigating treatments for HER2+ breast cancer and triple-negative breast cancer (TNBC), combining neratinib with everolimus (an mTOR inhibitor) or trametinib (a MEK inhibitor) significantly enhanced tumor growth inhibition compared to using neratinib alone, achieving up to 81% inhibition in xenograft models.

The combination therapies not only improved anti-tumor effects but also activated apoptosis pathways, indicating a potential mechanism for their enhanced efficacy, making these combinations promising options for treating these aggressive breast cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PI3K and MAPK Pathways as Targets for Combination with the Pan-HER Irreversible Inhibitor Neratinib in HER2-Positive Breast Cancer and TNBC by Kinome RNAi Screening. Lee, J., Liu, H., Pearson, T., et al.[2021]

In a study of 36 patients with BRAF V600E-mutant anaplastic thyroid cancer, the combination of dabrafenib and trametinib showed a significant overall response rate of 56%, with three patients achieving complete responses.

The treatment demonstrated manageable safety, with no new adverse effects identified, and improved median progression-free survival of 6.7 months and overall survival of 14.5 months, indicating it is a promising option for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study. Subbiah, V., Kreitman, RJ., Wainberg, ZA., et al.[2022]

In a study of 247 patients with metastatic hormone receptor-positive, PIK3CA-mutant breast cancer, 61.5% developed any-grade hyperglycemia after treatment with alpelisib, with a median onset time of just 16 days.

Patients receiving alpelisib as standard care experienced significantly higher rates of hyperglycemia compared to those in clinical trials, highlighting the importance of monitoring and optimizing glycemic status before starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. Shen, S., Chen, Y., Carpio, A., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.e18149

Pilot study evaluating the addition of cemiplimab in BRAF ... Pilot study evaluating the addition of cemiplimab in BRAF-mutant anaplastic thyroid cancer after progression on dabrafenib and trametinib.

2. clinicaltrials.gov clinicaltrials.gov/study/nct06902376

XL092 and Cemiplimab in BRAF WT Thyroid Cancer This study includes subjects with BRAFV600E wild type (WT) anaplastic thyroid cancer (ATC) who are scheduled to undergo surgical resection as part of their ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04238624

NCT04238624 | Study of Cemiplimab Combined With ... This study is being done to see if adding the study drug, cemiplimab, to the standard therapy with dabrafenib and trametinib is an effective treatment against ...

4. withpower.com withpower.com/trial/phase-1-thyroid-carcinoma-anaplastic-5-2025-14bac

XL092 + Cemiplimab for Thyroid Cancer 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, ...

5. unclineberger.org unclineberger.org/news/unc-lineberger-launches-groundbreaking-trial-for-rare-aggressive-thyroid-cancer/

UNC Lineberger launches groundbreaking trial for rare ... The trial is designed to offer hope to the almost 60% of ATC patients without a BRAF mutation and are often excluded from existing targeted ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06902376

NCT06902376 | XL092 and Cemiplimab in BRAF WT ... The study hypothesizes that the combination of neoadjuvant XL092 and cemiplimab will be safe and feasible prior to surgical resection in participants with BRAF ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12020464/

Anticancer drug therapy for anaplastic thyroid cancer Combination therapy with a BRAF inhibitor and MEK inhibitor has shown encouraging efficacy in patients with BRAF V600E-mutated anaplastic thyroid cancer.

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-01421

XL092 and Cemiplimab for the Treatment of BRAF V600E- ... Giving XL092 and cemiplimab before and after surgery may be safe, tolerable and/or effective in treating patients with BRAF V600E wild type anaplastic thyroid ...