In this Phase II trial of personalized immunotherapy in R/M HNSCC, gene expression of LAG3 and CTLA4 by RNA seq will be determined to select the appropriate agent (Ipilimumab or Relatlimab) to add to Nivolumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) who have failed prior immunotherapy with anti-PD-1 or PD-L1 mAb therapy. The agent, either Ipilimumab or Relatlimab will be chosen based on the highest relevant immune gene expression (CTLA4 or LAG-3) as long as the minimum difference required is met.
In this Phase II non-randomized trial, n=40 eligible patients will have tumor tissue (core or excisional/incisional) for gene expression of LAG3 and CTLA4 via RNA seq per OmniSeq Immune Report Card to determine which drug (either Relatlimab or Ipilimumab) will be added to Nivolumab for treatment. The patient will then receive the prescribed therapy continuously for up to 24 cycles (1 cycle = 28 days). The drug to be added to Nivolumab will be based on which relevant gene has the highest expression as long as the minimum difference required is met. If the minimum difference is not met than a patient will be randomized to either Nivolumab plus Relatlimab or Nivolumab plus Ipilimumab. The patient will then receive the prescribed therapy continuously for up to 24 cycles (1 cycle = 28 days) with repeat imaging prior to every 3rd cycle until progression of disease. Response, evaluated by RECIST 1.1, with modifications to allow for continued therapy until progressive disease is confirmed if the patient is clinically stable, will be used in the trial. If the patient has confirmed progression the patient may be eligible to undergo a second biopsy and second treatment on trial. If these criteria are met the patient will then be treated with this new combination with repeat imaging prior to every 3rd cycle as per initial treatment, until progression of disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
IV administration of both Nivolumab and Relatlimab
IV administration of both Nivolumab and Ipilimumab
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
Probability of Objective Response (OR) - Selected Treatment
The probability of response to therapy in patients who have progressed on prior immunotherapy. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is disappearance of all target and non-target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From start of treatment, up to 36 months
Probability of Objective Response (OR) - Randomized Treatment
The probability of response to therapy in patients who have progressed on prior immunotherapy. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is disappearance of all target and non-target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From start of treatment, up to 36 months
Disease Control Rate (DCR)
The percent probability of not experiencing disease progression in patients regardless of selected/randomized treatment. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is disappearance of all target and non-target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Stable Disease (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions.
Time frame: From start of treatment, up to 36 months
Progression-free Survival (PFS)
The length of time from the start of treatment that patients live with disease that does not progress per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) in patients who have progressed on prior immunotherapy. Per RECIST, Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions compared to baseline sum of target lesions, or any new lesions.It also includes the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: From start of treatment up to 36 months
Overall Survival (OS)
The length of time from the start of treatment that patients remain alive, in patients who have progressed on prior immunotherapy.
Time frame: From start of treatment, up to 36 months
Duration of Disease Control
Mean number of months that patients who had Stable Disease experienced disease control. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Stable Disease (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions.
Time frame: From start of treatment, up to 36 months
Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Adverse Events possibly, probably or definitely related to study treatment per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 experienced.
Time frame: From start of treatment, up to 36 months
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