Chemotherapy + Pembrolizumab for Head and Neck Cancer

Overseen By Jennifer Ruth, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dan Zandberg

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Autoimmune disease, Pneumonitis, 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: 9

Duration: Approximately 9 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new sequence of chemotherapy combined with pembrolizumab, a drug that boosts the immune system, for treating head and neck cancer. Researchers believe altering the timing of chemotherapy might enhance treatment effectiveness. The trial targets individuals with recurrent or metastatic head and neck cancer that cannot be cured with local treatments. Participants should not have previously received certain types of cancer drugs for their condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on systemic steroids or immunosuppressive agents for an active autoimmune disease, you may not be eligible to participate.

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

Research has shown that combining pembrolizumab, carboplatin, and paclitaxel is generally safe for treating certain cancers, such as head and neck cancer. Studies indicate that most patients, even those with extensive prior treatments, tolerate this combination well. The treatment effectively manages cancer while maintaining an acceptable safety level.

Though side effects may occur, they are usually manageable, allowing patients to continue treatment as planned. For those considering joining a trial with this treatment, these findings suggest it has been safe for previous patients in similar situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Unlike the standard treatments for head and neck cancer, which often focus on either chemotherapy or immunotherapy alone, this combination of pembrolizumab with carboplatin and paclitaxel stands out by integrating both approaches. Pembrolizumab is an immunotherapy that boosts the body's immune response specifically against cancer cells, while carboplatin and paclitaxel are chemotherapies that directly target and kill cancer cells. This dual approach could potentially enhance the overall effectiveness of treatment by attacking the cancer on two fronts. Researchers are excited because this combination may improve outcomes for patients by increasing the chances of shrinking tumors and prolonging survival.

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

In this trial, participants will receive a combination of pembrolizumab, carboplatin, and paclitaxel. Research has shown that this combination is promising for treating head and neck cancer. Studies have found that it can improve outcomes for patients with head and neck squamous cell carcinoma (HNSCC). Specifically, patients demonstrated significant antitumor activity, indicating that the treatment effectively targets and reduces cancer cells. The treatment also maintains a manageable safety profile, allowing most people to tolerate the side effects. This approach aims to enhance the immune system's response to cancer while using chemotherapy to directly attack cancer cells. ^{1 2 6 7}

Who Is on the Research Team?

Dan P. Zandberg

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

Adults with recurrent or metastatic head and neck squamous cell carcinoma, not curable by local therapies. Participants must have a certain level of platelets, normal organ/marrow function, no severe allergies to trial drugs, and no recent immunotherapy or chemotherapy for this condition. They should be in relatively good health (ECOG PS 0-2) and willing to use contraception.

Inclusion Criteria

AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN (≤ 5 X the institutional ULN for patients with liver metastasis)

My head or neck cancer has returned or spread and cannot be cured with surgery or radiation.

I am willing to use birth control or abstain from sex during and for 60 days after the study.

Exclusion Criteria

I haven't had systemic therapy for recurrent/metastatic cancer but may have had platinum-based therapy over 6 months ago for advanced HNSCC with curative intent.

I haven't had PD-1 or PD-L1 therapy for recurrent/metastatic disease, but it's been over a year if I had it for local disease.

I have had lung inflammation treated with steroids or have a lung condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg IV every 3 weeks, with carboplatin and paclitaxel starting from cycle 2 and given every 3rd cycle for a total of 4 cycles

Approximately 9 months

Every 3 weeks for pembrolizumab, every 9 weeks for carboplatin/paclitaxel

Maintenance

Pembrolizumab maintenance at 400 mg IV every 6 weeks for 12 cycles

2 years

Every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab

Trial Overview

The trial is testing a new way of giving chemotherapy in short bursts (pulsed dose) plus Pembrolizumab. The idea is that standard chemo might weaken the immune system too much when given with Pembrolizumab, an anti-PD-1 mAb therapy. This study will see if pulsed chemo works better after the mAb treatment.

How Is the Trial Designed?

Group I: Pembrolizumab + Carboplatin with Paclitaxel Experimental Treatment 3 Interventions

Pembrolizumab: Administer 200 mg intravenously (IV) every 3 weeks (q3w); maintenance will be continued at 400 mg IV q6w for 12 cycles for a total of 2 years of therapy Carboplatin: Started with cycle 2 (C2) of pembrolizumab and continued thereafter every 3rd cycle of pembrolizumab for a total of 4 cycles with paclitaxel; carboplatin will be given at C2, C5, C8, and C11 of pembrolizumab. Paclitaxel: Started with cycle 2 (C2) of pembrolizumab and continued thereafter every 3rd cycle of pembrolizumab for a total of 4 cycles with carboplatin.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Dan Zandberg

Lead Sponsor

Trials

7

Recruited

330+

Published Research Related to This Trial

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]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has shown significant overall response rates and survival benefits in patients with recurrent or metastatic head and neck squamous cell carcinoma compared to chemotherapy alone, particularly in populations with high PD-L1 expression (CPS ≥ 20 and CPS ≥ 1).

The safety profile of pembrolizumab is comparable to other PD-1/PD-L1 inhibitors, with common side effects including diarrhea and hypothyroidism, but it has a favorable toxicity profile compared to the EXTREME chemotherapy regimen, highlighting the importance of PD-L1 scoring for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. Desilets, A., Soulières, D.[2022]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

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