New chemotherapy approach with pembrolizumab for advanced head and neck cancer

Phase II Trial of Pulsed Dose Chemotherapy Plus Pembrolizumab in the First Line Treatment of Recurrent/Metastatic HNSCC

This study is testing a new way to give chemotherapy with pembrolizumab for patients with advanced head and neck cancer to see if it works better and is easier to tolerate than standard treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pittsburgh (other)
• Drugs / interventions: pembrolizumab, radiation, chemotherapy, immunotherapy
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT06052839 on ClinicalTrials.gov

What this trial studies

This trial investigates a novel sequence of pulsed dose chemotherapy combined with pembrolizumab for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The study aims to improve treatment efficacy by administering pembrolizumab before chemotherapy, which may enhance the immune response and reduce immunosuppression associated with standard treatment regimens. Patients will receive pembrolizumab followed by carboplatin and paclitaxel, with the goal of maximizing therapeutic synergy and improving tolerability. The trial also explores the potential applicability of this approach to other solid tumors.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with recurrent or metastatic head and neck squamous cell carcinoma that is not amenable to local therapies and has a PD-L1 Combined Positive Score greater than 1.

Not a fit: Patients with early-stage head and neck cancer or those whose cancer can be treated with local therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could lead to improved outcomes and better tolerability for patients with advanced head and neck cancer.

How similar studies have performed: While this approach is innovative, similar studies combining immunotherapy with chemotherapy have shown promise, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Recurrent/metastatic squamous cell carcinoma of the head and neck that is considered incurable by local therapies.
2. PD-L1 Combined Positive Score (CPS) \>1
3. Age \> 18 years.
4. Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) 0-2
5. Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) 1
6. Patients must have normal organ and marrow function as defined below:

   1. absolute neutrophil count ≥1,000/mcL
   2. platelets ≥100,000/mcL
   3. total bilirubin ≤ 1.5 X the institutional upper limit of normal (ULN)
   4. AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN (≤ 5 X the institutional ULN for patients with liver metastasis)
   5. Creatinine clearance ≥40 mL/min/1.73 m2 for patients with a creatinine levels above institutional normal.
7. Female subjects of childbearing potential should have a negative urine or serum pregnancy during the screening period and also prior to receiving the first dose of study medication. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
8. Female subjects of childbearing potential should be willing to use one methods of birth control or abstain from heterosexual activity for the course of the study through 60 days after the last dose of study medication. Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
9. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 60 days after the last dose of study therapy.
10. Ability to understand and the willingness to sign a written informed consent document.
11. If known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on MRI/CT evaluation done within 30 days of consent.

Exclusion Criteria:

1. Patients should not have had prior systemic therapy alone administered in the recurrent/ or metastatic setting. If a patient received platinum based systemic therapy which was completed more than 6 months prior to signing consent given as part of multimodal curative intent treatment for locally advanced HNSCC (This includes both definitive concurrent chemoradiation and adjuvant chemoradiation) the patient is still eligible,
2. A patient cannot have received prior anti-PD-1 or anti-PD-L1 monoclonal antibody (mAb) therapy as systemic therapy for the treatment of recurrent/metastatic disease. Patients that received anti-PD-1 or anti-PD-L1 mAb therapy as part of multimodality curative intent treatment of locally advanced disease are still eligible as long as it has been at least 1 year since prior therapy. Patients that received anti-PD-1 or anti-PD-L1 mAb therapy as part of radiation for locoregional recurrence will be eligible as long as it has been 1 year since prior therapy.
3. Squamous cell carcinoma of the skin or of salivary gland origin.
4. Has an active autoimmune disease requiring systemic treatment within the past 3 months, or a syndrome that requires ongoing systemic steroids or immunosuppressive agents. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism or Sjogren's syndrome will not be excluded from the study.
5. Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis.
6. Prior malignancy within 2 years that in the investigator's opinion would be likely to affect the outcomes of the patients R/M HNSCC.
7. Peripheral sensory neuropathy \> grade 2 by CTCAE v5.0
8. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
9. Known allergy or hypersensitivity to carboplatin, other platinum agents, pembrolizumab, or paclitaxel.
10. Baseline neutrophil count of \< 1,500 cells/mm.

Where this trial is running

Pittsburgh, Pennsylvania

• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Dan P Zandberg, MD — UPMC Hillman Cancer Center
• Study coordinator: Jennifer Ruth, RN, BSN

Conditions: Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, CD8 tumor infiltrating lymphocyte, interferon gamma, anti-PD-1 mAb