This multicenter, open-label, randomized phase 3 trial will determine if palbociclib and cetuximab (Arm 1) improves overall survival (OS) in comparison to cetuximab monotherapy (Arm 2) in patients with CDKN2A-altered, HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who experienced disease progression on a PD-1/L1 inhibitor (given as monotherapy or in combination with other therapy).
Histologically or cytologically confirmed RM-HNSCC that is HPV-unrelated disease; defined as SCC of the oral cavity, larynx, or hypopharynx and p16 negative SCC of the oropharynx or p16 negative non-cutaneous SCC unknown primary of the neck.
CDKN2A loss-of-function (LOF) alteration: mutation or homozygous deletion described on genomic sequencing report.
Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam, per RECIST 1.1.
Disease progression on a PD-1/L1 inhibitor-containing regimen (given as monotherapy or in combination with other therapy).
Prior treatment with cetuximab for recurrent or metastatic disease (however, prior cetuximab given as a component of multimodality therapy for newly diagnosed, locally advanced, non-metastatic HNSCC is allowable).
Prior treatment with a CDK4/6 inhibitor for RM-HNSCC.
Rb (retinoblastoma) loss: mutation or homozygous deletion described on genomic sequencing report.
Currently receiving any other investigational agents.
Parallel
Palbociclib
DrugAdministered on an outpatient basis
Cetuximab
DrugGiven intravenously over approximately 60 minutes
Overall survival (OS)
-Defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise.
Overall response rate (ORR) - (complete response + partial response)
* Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Duration of response (DoR)
-The duration of response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Progression-free survival (PFS)
* Defined as the days from the date of treatment start to progression or death. The alive patients without progression are censored at the last follow-up. * Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. ): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Frequency of adverse events
-Will be measured by CTCAE v. 5.0
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Washington University School of Medicine
Lead sponsor
Pfizer
Collaborator
The Joseph Sanchez Foundation
Collaborator
