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

24 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Avelumab, Cetuximab, and Palbociclib for head and neck cancer?

Research suggests that Avelumab, which targets the PD-L1 protein to help the immune system attack cancer cells, and Cetuximab, which blocks a protein that helps cancer cells grow, may be effective in treating head and neck cancer. Although specific effectiveness data for the combination with Palbociclib is not provided, these drugs have shown potential in similar treatments. ^{1 2 3 4 5}

Is the combination of avelumab, cetuximab, and palbociclib safe for humans?

A study tested the safety of combining avelumab, cetuximab, and palbociclib in patients with head and neck cancer, indicating that research is being conducted to evaluate their safety together. ^{1 2 5 6 7}

What makes the drug combination of Avelumab, Cetuximab, and Palbociclib unique for head and neck cancer?

This drug combination is unique because it combines avelumab, which blocks PD-L1 to help the immune system attack cancer cells, with cetuximab, an EGFR inhibitor that targets cancer cell growth, and palbociclib, a CDK4/6 inhibitor that stops cancer cells from dividing. This multi-targeted approach is being tested for its safety and effectiveness in treating recurrent or metastatic head and neck cancer, offering a novel strategy compared to traditional chemotherapy. ^{1 2 5 6 8}

What is the purpose of this trial?

The purpose of the study is to find out if the study drugs Avelumab, Cetuximab, and Palbociclib will slow or stop your cancer from getting worse, and whether it causes side effects. The second purpose is to measure whether your cancer responds to the study drugs Avelumab, Cetuximab, and Palbociclib. The study drugs Avelumab, Cetuximab, and Palbociclib are types of drugs called a monoclonal antibody. Monoclonal antibodies are made to recognize, target, and bind to specific proteins on cells the building blocks making up your tissues.

Research Team

Kathryn A Gold, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

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

You have tumors that can be measured according to specific 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.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

References

1. England 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. [2023]

2. England 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. [2022]

3. Germany 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. [2021]

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

mTOR co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations. [2022]

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

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

6. Switzerland 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. [2022]

7. England 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. [2023]

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

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis. [2015]