A Randomized, Double-blind, Placebo-controlled Phase 3 Study to evaluate GSK4057190A as Sequential Therapy after Chemoradiation in Participants with Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma

PI: Prof.ssa Lisa Licitra 

The JADE 221530 study is an international clinical trial evaluating the activity of Dostarlimab as a sequential therapy following definitive concurrent chemoradiotherapy in patients with locally advanced, unresected squamous cell carcinoma of the head and neck. 

Dostarlimab is a humanized anti-PD-1 (Programmed Death-1) monoclonal antibody, which targets the programmed cell death receptor 1, leading to the destruction of cancer cells. 

This study, conducted in compliance with international ethical guidelines, is considered experimental, as the investigational drug Dostarlimab has not yet been approved by health authorities for head and neck cancer. 
Specifically, given the current lack of additional therapies following chemoradiation, this study proposes to evaluate the efficacy of Dostarlimab compared to placebo in patients who have completed concurrent chemoradiotherapy. 

By adding Dostarlimab after chemoradiotherapy, the goal of the study is to improve patient outcomes by reducing the risk of cancer recurrence (either locally or at distant sites), preventing the need for surgery, and ultimately improving event-free survival (EFS)—defined as the absence of complications or death related to the tumor. 

Eligibility for enrollment in the study depends on: patient characteristics (such as demographic data, cancer history, and comorbidities), laboratory tests, and radiological parameters. These will be assessed through specific screening procedures before treatment begins. All tests will be conducted at this Institution according to clearly defined timelines. 

Additionally, eligible patients must have a diagnosis of stage III–IVA squamous cell carcinoma of the head and neck that expresses the PD-L1 protein. During the screening phase, tumor tissue will be analyzed for the PD-L1 biomarker (Programmed Death-Ligand 1), and for HPV (Human Papillomavirus) if the tumor originates from the oropharynx. These analyses may be performed on a stored biological sample, such as the biopsy taken prior to the start of chemoradiotherapy. 

Assignment to one of the two study arms (active treatment with Dostarlimab vs. placebo) will be carried out through a computerized process known as randomization, which means patients are randomly assigned to a group, without influence or choice from the study doctor or the patient. Furthermore, the assignment will be double-blind, meaning neither the patient nor the study doctor will know which treatment is being administered. 

The study design includes: 

• Arm A: Dostarlimab, administered intravenously (i.e., via infusion) every 3 weeks; 
• Arm B: Placebo (a saline solution with no active drug), also administered intravenously every 3 weeks. 

Treatment will continue for up to one year. Afterward, all participants will be monitored by the study doctor to assess whether the cancer recurs. 

Patients will also be monitored for potential immune-mediated toxicities, which may occur due to the overstimulation of the immune system by immunotherapy. These adverse events are often known side effects, where the immune system mistakenly attacks not only diseased cells but also healthy ones, no longer recognizing them as "self." In such cases, the study team will propose symptomatic treatments and implement strategies to reduce the severity of these effects (e.g., treatment pauses, corticosteroid therapies, etc.). To ensure their safety, particularly regarding the described risks, participants will be closely monitored. 

Treatment will proceed for up to 11 administrations and will only be discontinued in the event of disease progression, unacceptable toxicity, or— as is always the case in a clinical trial— if the investigator or patient decides to withdraw. In any case, patients will continue to have access to medical care and will not forfeit any legal rights or benefits to which they are entitled. 

The study staff is available for more detailed information (email: amo@istitutotumori.mi.it).