Avelumab + Cetuximab + Palbociclib for Head and Neck Cancer

Overseen By Kathryn A Gold, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kathryn Gold

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Other malignancies, HIV, Hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of three drugs—Avelumab (Bavencio), Cetuximab, and Palbociclib—can slow or stop the progression of head and neck cancer. Researchers aim to determine any side effects and assess the cancer's response to these drugs. The drugs target specific proteins on cancer cells. This trial may suit individuals with squamous cell carcinoma of the head and neck that cannot be treated with surgery or radiation. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain immunosuppressant therapies or have had recent chemotherapy or monoclonal antibody treatments.

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

Research has shown that the combination of avelumab, cetuximab, and palbociclib is well tolerated by patients with head and neck cancer. These studies focused on patients whose cancer had returned or spread after treatment and found that this combination was generally safe. Most importantly, researchers observed that patients could handle the treatment without major problems. These findings suggest that the combination is safe enough for further testing in other patients with similar conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of avelumab, cetuximab, and palbociclib for head and neck cancer because it targets the disease in a novel way. Unlike standard treatments that typically focus on either chemotherapy or radiation, this investigational treatment utilizes a blend of immunotherapy (avelumab) and targeted therapies (cetuximab and palbociclib). Avelumab helps the immune system recognize and attack cancer cells, cetuximab blocks signals that encourage cancer cell growth, and palbociclib inhibits proteins that allow cancer cells to multiply. This multi-pronged approach aims to enhance treatment effectiveness and overcome resistance that often develops with standard therapies.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that a combination of three drugs—avelumab, cetuximab, and palbociclib—may help treat head and neck cancer. This trial will administer this combination to participants to determine the maximum tolerated dose or recommended phase II dose. Previous studies found that patients with recurring or spreading head and neck cancer tolerated these drugs well. These medications work together to attach to specific proteins on cancer cells, potentially stopping or slowing the cancer's growth. Early results suggest this combination could be more effective than other treatments for patients whose cancer cannot be cured with surgery or radiation. While more research is needed, the initial findings are promising for those considering this treatment option. ^{1 2 4 5 6}

Who Is on the Research Team?

Kathryn A Gold, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for people with certain types of head and neck cancer that can't be cured by surgery or radiation. Participants must have a life expectancy over 12 weeks, good blood, liver, and kidney function, not be pregnant if capable of bearing children, and have tumors that can be measured.

Inclusion Criteria

My blood, liver, and kidney functions are all within normal ranges.

My cancer in the head or neck area cannot be cured with surgery or radiation.

You have tumors that can be measured according to specific criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive avelumab, cetuximab, and palbociclib in 28-day cycles with a dose escalation design

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Cetuximab
• Palbociclib

Trial Overview The study tests whether the drugs Avelumab, Cetuximab, and Palbociclib slow down or stop cancer growth in patients with recurrent or metastatic head and neck squamous cell carcinoma. These drugs are monoclonal antibodies designed to target specific proteins on cancer cells.

How Is the Trial Designed?

Group I: Avelumab, Palbociclib, and Cetuximab Experimental Treatment 3 Interventions

Identify the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) for the combination of palbociclib, avelumab, and cetuximab

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Kathryn Gold

Lead Sponsor

Trials

1

Recruited

20+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a study involving 32 patients with advanced head and neck cancer, the addition of cetuximab to a treatment regimen of paclitaxel, carboplatin, and radiation was found to increase dermatologic toxicities, with 44% experiencing grade 3 radiation dermatitis.

Despite the increased skin toxicity, the combination treatment did not lead to higher mucosal toxicity compared to previous studies, suggesting that while cetuximab may enhance side effects, it does not worsen certain other adverse effects associated with cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis. Birnbaum, A., Dipetrillo, T., Rathore, R., et al.[2015]

The study investigates the safety and efficacy of combining avelumab, an anti-PD-L1 monoclonal antibody, with cetuximab in patients with recurrent or metastatic squamous cell head and neck carcinoma, aiming to improve outcomes beyond the current standard of care.

Up to 16 participants will be enrolled in this phase II trial to assess the safety of the drug combination and determine the optimal dose of cetuximab, with secondary objectives focusing on tumor response and overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for the EACH trial: a multicentre phase II study evaluating the safety and antitumour activity of the combination of avelumab, an anti-PD-L1 agent, and cetuximab, as any line treatment for patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC) in the UK. Ng, K., Metcalf, R., Sacco, J., et al.[2023]

In a study of 134 patients with recurrent and/or metastatic head and neck cancer, the addition of cetuximab (Cx) to platinum-based and 5-fluorouracil chemotherapy (PFU) significantly improved progression-free survival (PFS) from 4.4 months to 6.1 months.

The presence of the KRAS-LCS6 variant did not have a prognostic impact on treatment outcomes, indicating that the PFU+Cx combination may be beneficial for all patients regardless of their KRAS variant status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit of cetuximab addition to a platinum-fluorouracil-based chemotherapy according to KRAS-LCS6 variant in an unselected population of recurrent and/or metastatic head and neck cancers. Bastit, V., Bon-Mardion, N., Picquenot, JM., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

The combination of the CDK4/6 inhibitor palbociclib with the EGFR inhibitor cetuximab and the PD-L1 inhibitor avelumab was found to be well tolerated in patients with recurrent/metastatic head and neck squamous cell carcinoma, with common side effects being rash and fatigue.

The study identified a recommended phase II dose of palbociclib at 125 mg, and showed an overall response rate of 42% with a median progression-free survival of 6.5 months, indicating potential efficacy for this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of avelumab, palbociclib, and cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma. Dennis, MJ., Sacco, AG., Qi, Y., et al.[2022]

In a study of adult patients with metastatic head and neck squamous cell cancer, substituting 5-fluorouracil (5-FU) with a taxane in a pembrolizumab-based treatment regimen did not increase toxicity or worsen survival outcomes.

Patients receiving the taxane combination experienced significantly lower rates of mucositis and elevated creatinine levels compared to those on the 5-FU regimen, indicating a better safety profile for the taxane approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer. Lee, B., Chehab, SS., Fan, W., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36279618/

A phase I study of avelumab, palbociclib, and cetuximab in ... Conclusions: The combination of avelumab, cetuximab, and palbociclib was well tolerated and supports further evaluation in patients with R/M HNSCC. Clinical ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03498378

Avelumab, Cetuximab, and Palbociclib in Recurrent or ... This study will enroll patients with head and neck squamous cell carcinoma not amenable to curative intent therapy. Treatment will be administered in 28 day ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1368837522005085

A phase I study of avelumab, palbociclib, and cetuximab in ... The combination of avelumab, cetuximab, and palbociclib was well tolerated and supports further evaluation in patients with R/M HNSCC.

4. cancer.gov cancer.gov/clinicaltrials/NCI-2018-01896

Avelumab, Palbociclib, and Cetuximab in Treating Patients ... Giving avelumab, palbociclib, and cetuximab may work better in treating patients with recurrent or metastatic head and neck squamous cell cancer. Eligibility ...

5. researchgate.net researchgate.net/publication/364618033_A_phase_I_study_of_avelumab_palbociclib_and_cetuximab_in_patients_with_recurrent_or_metastatic_head_and_neck_squamous_cell_carcinoma

A phase I study of avelumab, palbociclib, and cetuximab in ... A phase I study of avelumab, palbociclib, and cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma · Abstract.

6. clinicaltrial.be clinicaltrial.be/en/details/7432?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Avelumab, Cetuximab, and Palbociclib in Recurrent or Meta... This study will enroll patients with head and neck squamous cell carcinoma not amenable to curative intent therapy. Treatment will be ...