This is a feasibility trial studying anti-PD-1 therapy (Pembrolizumab) among patients with R/M HNSCC, delivered with ultrasound-induced microbubble cavitation, with the goal of optimizing delivery of Pembrolizumab and tumor response to Pembrolizumab. Patients will undergo 3 infusions of Pembrolizumab plus Definity 3 weeks apart. Following each infusion, ultrasound will be directed at the primary tumor site to induce microbubble cavitation, with the goal of tumor sonoporation. The primary endpoints will be feasibility, measured based on successful recruitment of 6 participants within 1 year of initiating recruitment, with successful completion of trial procedures among at least 80 percent of patients. Secondary endpoints will include proportion of serious adverse events, clinical/radiographic response, overall survival, and progression-free survival.
Pathologically confirmed, HPV-negative, R/M HNSCC per American Joint Committee on Cancer (AJCC) 8th Edition Staging Criteria, with CPS score > 1
The target lesion is ultrasound-accessible, biopsy-accessible, and measurable in at least one dimension, based on RECISTv1.1 criteria.
Male or female, aged ≥18 years of age
ECOG Performance status 0-2.
Patients with HPV-positive or p16-positive SCC
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or antiCTLA-4 antibody
Any history of allergy to the study drug components, including to polyethyleneglycol or medications containing polyethylene glycol.
Patients with a known history of anatomic right-to-left, bi-directional, or transient right-to-left cardiac shunts
Single group
Pembrolizumab
DrugPembrolizumab will be administered intravenously at a dose of 200 mg every 3 weeks for up to 3 cycles
Definity
DrugDefinity will be administered intravenously during each treatment cycle to facilitate ultrasound-induced microbubble cavitation.
Ultrasound-Induced Microbubble Cavitation
DeviceTherapeutic Ultrasound will be applied to the tumor site during and following the Definity infusion to induce microbubble cavitation using modified ultrasound parameters.
Number of Participants who complete all planned treatment cycles
The number of participants who completed trial procedures among at least 80 percent of patients, among patients with recurrent or metastatic head and neck squamous cell carcinoma.
Number of Treatment-Related Adverse Events (TRAEs)
Number of adverse events related to study treatment, assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Objective Response Rate using RECIST v1.1
Objective Response Rate (ORR) will be assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). The number of participants who achieve a Complete Response (CR)-disappearance of all target lesions, Partial Response (PR)-at least a 30% reduction in tumor size from baseline, Progressive Disease (PD)--At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and Stable Disease (SD)--Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, will be reported. ORR measured using the RECISTv1.1 criteria or assessment of clinical and pathologic response.
Overall Survival
Time from treatment start until death from any cause.
Disease-Free Survival
Time from treatment start until recurrence of disease or death from any cause, whichever occurs first.
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Thomas Jefferson University
Lead sponsor
Lantheus Medical Imaging
Collaborator
